Compounds useful as reversible inhibitors of cathepsin S

ABSTRACT

Disclosed are cathepsin S reversible inhibitory compounds of the formulas (I), (Ia) and (II), (IIa) as defined herein. The compounds are useful for treating autoimmune diseases. Also disclosed are processes for making such novel compounds.

CONTINUING APPLICATION DATA

[0001] This is a divisional application of U.S. application Ser. No.10/082,952.

TECHNICAL FIELD OF THE INVENTION

[0002] This invention relates to peptidyl cysteine protease inhibitors.The compounds are reversible inhibitors of the cysteine proteasecathepsin S and are therefore useful in the treatment of autoimmunediseases. The invention also relates to processes for preparing suchcompounds and pharmaceutical compositions comprising them.

BACKGROUND OF THE INVENTION

[0003] Cathepsin S is a member of the papain family, within the papainsuperfamily of cysteine proteases. The papain family is the largestgroup of cysteine proteases and includes proteases such as cathepsins B,H, K, L, O and S. (A. J. Barrett et al., 1996, Perspectives in DrugDiscovery and Design, 6, 1). The cysteine proteases have important rolesin human biology and diseases including atherosclerosis, emphysema,osteoporosis, chronic inflammation and immune disorders (H. A. Chapmanet al., 1997, Ann. Rev. Physiol., 59, 63). Cathepsin S plays a key rolein regulating antigen presentation and immunity (H. A. Chapman, 1998,Current Opinion in Immunology, 10, 93; R. J. Riese et al., 1998, J.Clin. Invest., 101, 2351; R. J. Riese et al., 1996, Immunity, 4, 357).

[0004] The specificity of the immune response relies on processing offoreign protein and presentation of antigenic peptide at the cellsurface. Antigenic peptide is presented bound to MHC Class II, aheterodimeric glycoprotein expressed in certain antigen presenting cellsof hematopoietic lineage, such as B cells, macrophages and dendriticcells. Presentation of antigen to effector cells, such as T-cells, is afundamental step in recognition of non-self and thus initiation of theimmune response.

[0005] Recently MHC Class II heterodimers were shown to associateintracellularly with a third molecule designated invariant chain.Invariant chain facilitates Class II transport to the endosomalcompartment and stabilizes the Class II protein prior to loading withantigen. Invariant chain interacts directly with Class II dimers in theantigen-binding groove and therefore must be proteolyzed and removed orantigen cannot be loaded or presented. Current research suggests thatinvariant chain is selectively proteolyzed by cathepsin S, which iscompartmentalized with MHC Class II complexes within the cell. CathepsinS degrades invariant chain to a small peptide, termed CLIP, whichoccupies the antigen—binding groove. CLIP is released from MHC Class IIthe interaction MHC Class II with HLA-DM, a MHC-like molecule thusfreeing MHC Class II to associate with antigenic peptides. MHC ClassII-antigen complexes are then transported to the cell surface forpresentation to T-cells, and initiation of the immune response.Cathepsin S, through proteolytic degradation of invariant chain to CLIP,provides a fundamental step in generation of an immune response. Itfollows that inhibition of antigen presentation via prevention ofinvariant chain degradation by cathepsin S could provide a mechanism forimmuno-regulation. Control of antigen-specific immune responses has longbeen desirable as a useful and safe therapy for autoimmune diseases.Such diseases include Crohn's disease and arthritis, as well as otherT-cell-mediated immune responses (C. Janeway and P. Travers, 1996,Immunobiology, The Immune System in Health and Disease, Chapter 12).Furthermore, cathepsin S, which has broad pH specificity, has beenimplicated in a variety of other diseases involving extracellularproteolysis, such as Alzheimer's disease (U. Muller-Ladner et al., 1996,Perspectives in Drug Discovery and Design, 6, 87) and atherosclerosis(G. K. Sukhova et al., 1998, J. Clin. Invest., 102, 576).

[0006] Cysteine proteases are characterized by having a cysteine residueat the active site which serves as a nucleophile. The active site alsocontains a histidine residue. The imidazole ring on the histidine servesas a base to generate a thiolate anion on the active site cysteine,increasing its nucleophilicity. When a substrate is recognized by theprotease, the amide bond to be cleaved is directed to the active site,where the thiolate attacks the carbonyl carbon forming an acyl-enzymeintermediate and cleaving the amide, liberating an amine. Subsequently,water cleaves the acyl-enzyme species regenerating the enzyme andliberating the other cleavage product of the substrate, a carboxylicacid.

[0007] A proposed mechanism of action of the cysteine proteaseinhibitors of this invention is that the inhibitors contain afunctionality that can react (reversibly or irreversibly) with theactive site cysteine. The reactive functionality is attached to apeptide or peptide mimic that can be recognized and accommodated by theregion of the protease surrounding the active site. The nature of boththe reactive functionality and the remaining portion of the inhibitordetermine the degree of selectivity and potency toward a particularprotease.

[0008] Examples of reactive functionalities that have been described (D.Rasnick, 1996, Perspectives in Drug Discovery and Design, 6, 47) oncysteine protease inhibitors include peptidyl diazomethanes, epoxides,monofluoroalkanes and acyloxymethanes, which irreversibly alkylate thecysteine thiol. Other irreversible inhibitors include Michael acceptorssuch as peptidyl vinyl esters and other carboxylic acid derivatives (S.Liu et al., J. Med Chem., 1992, 35, 1067) and vinyl sulfones (J. T.Palmer et al., 1995, J. Med Chem., 38, 3193).

[0009] Reactive functionalities that form reversible complexes with theactive site cysteine include peptidyl aldehydes (R. P. Hanzlik et al.,1991, Biochim. Biophys. Acta., 1073, 33), which are non-selective,inhibiting both cysteine and serine proteases as well as othernucleophiles. Peptidyl nitriles (R. P. Hanzlik et al., 1990, Biochim.Biophys. Acta., 1035, 62) are less reactive than aldehydes and thereforemore selective for the more nucleophilic cysteine proteases. Variousreactive ketones have also been reported to be reversible inhibitors ofcysteine proteases (D. Rasnick, 1996, ibid). In addition to reactingwith the nucleophilic cysteine of the active site, reactive ketones mayreact with water, forming a hemiketal which may act as a transitionstate inhibitor.

[0010] Examples of cathepsin S inhibitors have been reported previously.J. T. Palmer (U.S. Pat. No. 5,776,718, 1998) described reversiblepeptidyl sulfones as inhibitors of cysteine proteases includingcathepsin S. J. L. Klaus et al. (WO 9640737, 1996) described reversibleinhibitors of cysteine proteases including cathepsin S, containing anethylene diamine.

[0011] Additional peptidyl nitrites or peptidyl ketoheterocyles havebeen reported either as protease inhibitors or as having otherutilities. For example, both nitriles and ketoheterocycles are describedby B. A. Rowe et al. (U.S. Pat. No. 5,714,471, 1998) as proteaseinhibitors useful in the treatment of neurodegenerative diseases.Peptidyl nitrites are reported by B. Malcolm et al. (WO 9222570, 1992)as inhibitors of picomavirus protease. H. Saika et al. (WO 9512611,1995) report peptidyl nitrites among compounds having endothelinreceptor antagonist activity. B. J. Gour-Salin (Can. J. Chem., 1991, 69,1288) and T. C. Liang (Arch. Biochim. Biophys., 1987, 252, 626)described peptidyl nitrites as inhibitors of papain. D. W. Woolley etal. (J. Org. Chem., 1963, 28, 2012) described a peptidyl nitrile as achemical intermediate.

[0012] Peptidyl ketoheterocycles having protease inhibiting or otheractivities have been reported, include inhibitors of serine proteasesdescribed by R. D. Tung et al. (WO 9817679, 1998). Inhibitors of FactorXa have been described by C. K. Marlowe et al. (WO 9640744, 1996).Peptidyl ketoheterocycles useful in the treatment of thrombin relateddiseases have been described by M. Costanzo et al. (WO 9640742, 1996).

[0013] A reversible inhibitor presents a more attractive therapy thanirreversible inhibitors. Even compounds with high specificity for aparticular protease can bind non-target enzymes. An irreversiblecompound could therefore permanently inactivate a non-target enzyme,increasing the likelihood of toxicity. Furthermore, any toxic effectsresulting from inactivation of the target enzyme would be mitigated byreversible inhibitors, and could be easily remedied by modified or lowerdosing. Finally, covalent modification of an enzyme by an irreversibleinhibitor could potentially generate an antibody response by acting as ahapten.

[0014] In light of the above, there is a clear need for compounds whichreversibly and selectively inhibit cathepsin S, such inhibitors would beuseful in therapy for antigen-specific immune responses as well as forindications in which cathepsin S exacerbates disease throughextracellular activity.

BRIEF DESCRIPTION OF THE INVENTION

[0015] The work cited above supports the principle that inhibition ofcathepsin S and subsequent inhibition of antigen presentation will bebeneficial in the treatment of various disease states. It is thereforean object of this invention to provide novel compounds that inhibitantigen presentation by virtue of reversible inhibition of the cysteineprotease cathepsin S. It is a further object of the invention to providemethods for treating diseases and pathological conditions involvingimmune disorders such as rheumatoid arthritis. It is yet a furtherobject of the invention to provide processes for preparation of theabove-mentioned novel compounds.

DETAILED DESCRIPTION OF THE INVENTION

[0016] The invention provides novel compounds of the formula (I):

[0017] A is —C(Y)— or —SO₂—

[0018] Y is O, S or NR_(a) wherein R_(a) is selected from the groupconsisting of H, alkyl, aryl, alkoxy, aryloxy, alkylamino and arylamino;

[0019] R₁ is alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl or aminowherein R₁ is optionally substituted by one or more R_(b);

[0020] R_(b) is selected from the group consisting of alkyl, cycloalkyl,aryl, heterocyclyl, heteroaryl, alkoxy, aryloxy, alkoxycarbonyl,aryloxycarbonyl, alkanoyl, aroyl, alkanoyloxy, aroyloxy, carbamoylwherein the nitrogen atom may be independently mono or di-substituted byalkyl, aryl, heterocyclyl or heteroaryl, alkanoylamino, aroylamino,alkylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, arylthio wherein the sulfur atom may be oxidized to a sulfoxideor sulfone, ureido wherein either nitrogen atom may be independentlysubstituted by alkyl, aryl, heterocyclyl or heteroaryl,alkoxycarbonylamino, aryloxycarbonylamino, alkylcarbamoyloxy,arylcarbamoyloxy, alkylsulfonylamino, arylsulfonylamino,alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atommay be independently mono or di-substituted by alkyl, aryl, heterocyclylor heteroaryl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino andguanidino, R_(b) may be further optionally substituted by one or moreR_(c);

[0021] R_(c) is selected from the group consisting of alkyl, cycloalkyl,aryl, heterocycle, heteroaryl, arylalkyl, alkoxy, aryloxy, arylalkoxy,alkanoyl, aroyl, amino wherein the nitrogen atom may be independentlymono or di-substituted by alkyl, aryl, heterocyclyl or heteroaryl,halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino;

[0022] R₂ is H or alkyl;

[0023] R₃ is H, alkyl, cycloalkyl, aryl, heterocyclyl or heteroaryl,wherein R₃ is optionally substituted by one or more groups of theformula R_(d);

[0024] R_(d) is selected from the group consisting of alkyl, cycloalkyl,aryl, heterocyclyl, heteroaryl, alkoxy, aryloxy, arylalkoxy,alkoxycarbonyl, aryloxycarbonyl, alkanoyl, aroyl, alkanoyloxy, aroyloxy,carbamoyl wherein the nitrogen atom may be independently mono ordi-substituted by alkyl, aryl, heterocyclyl or heteroaryl,alkanoylamino, aroylamino, alkylthio wherein the sulfur atom may beoxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom maybe oxidized to a sulfoxide or sulfone, ureido wherein either nitrogenatom may be independently substituted by alkyl, aryl, heterocyclyl orheteroaryl, alkoxycarbonylamino, aryloxycarbonylamino,alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino,arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino whereinthe nitrogen atom may be independently mono or di-substituted by alkyl,aryl, heterocyclyl or heteroaryl, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino, R_(d) may be further optionallysubstituted by one or more R_(e);

[0025] R_(e) is selected from the group consisting of alkyl, cycloalkyl,aryl, arylalkyl, alkoxy, aryloxy, arylalkoxy, alkanoyl, aroyl, amino,halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino;

[0026] R₄ is H or alkyl;

[0027] R₅ is H, alkyl or cycloalkyl;

[0028] R₆ is H, alkyl, cycloalkyl, aryl, heterocyclyl or heteroaryl,wherein R₆ is optionally substituted by one or more groups of theformula R_(f);

[0029] R_(f) is selected from the group consisting of alkyl, cycloalkyl,aryl, heterocyclyl, heteroaryl, alkoxy, aryloxy, alkanoyl, aroyl,arylalkoxy, heteroarylalkoxy, alkoxycarbonyl, aryloxycarbonyl,alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom may beindependently mono or di-substituted by alkyl, aryl, heterocyclyl orheteroaryl, alkanoylamino, aroylamino, alkylthio wherein the sulfur atommay be oxidized to a sulfoxide or sulfone, arylthio wherein the sulfuratom may be oxidized to a sulfoxide or sulfone, arylalkylthio whereinthe sulfur atom may be oxidized to a sulfoxide or sulfone, ureidowherein either nitrogen atom may be independently substituted by alkyl,aryl, heterocyclyl or heteroaryl, alkoxycarbonylamino,aryloxycarbonylamino, alkylcarbamoyloxy, arylcarbamoyloxy,alkylsulfonylamino, arylsulfonylamino, alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom may be independentlymono or di-substituted by alkyl, aryl, heterocyclyl or heteroaryl,halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino,R_(f) may be further optionally substituted by one or more R_(g);

[0030] R_(g) is selected from the group consisting of alkyl, cycloalkyl,aryl optionally substituted by halogen, C1-5alkyl or C1-5alkoxy,heterocyclyl, heteroaryl, alkoxy, aryloxy, arylalkoxy, alkoxycarbonyl,aryloxycarbonyl, alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogenatom may be independently mono or di-substituted by alkyl, aryl,heterocyclyl or heteroaryl; alkanoylamino, aroylamino, alkylthio whereinthe sulfur atom may be oxidized to a sulfoxide or sulfone, arylthiowherein the sulfur atom may be oxidized to a sulfoxide or sulfone,ureido wherein either nitrogen atom may be independently substituted byalkyl, aryl, heterocyclyl or heteroaryl; alkoxycarbonylamino,aryloxycarbonylamino, alkylcarbamoyloxy, arylcarbamoyloxy,alkylsulfonylamino, arylsulfonylamino, alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom may be independentlymono or di-substituted by alkyl, aryl, heterocyclyl or heteroaryl;halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino;

[0031] or R₅ together with R₆ form a 3 to 6 membered carbocyclic ring,the carbocyclic ring being optionally substituted with one or moreR_(h);

[0032] R_(h) is selected from the group consisting of alkyl, aryl,alkoxycarbonyl, aryloxycarbonyl, arylalkoxycarbonyl, carbamoyl whereinthe nitrogen atom may be optionally mono or di-substituted with a groupselected from alkyl, cycloalkyl, aryl, arylalkyl, heterocyclyl orheteroaryl; halogen, hydroxy, carboxy and cyano;

[0033] R₇ is R₈—C(Z)-;

[0034] wherein Z is O, S, or NR_(i) wherein R_(i) is selected from thegroup consisting of H, alkyl, aryl, alkoxy, aryloxy and hydroxy;

[0035] R₈ is a 5-8 membered monocyclic heteroaryl or 8-11 memberedbicyclic heteroaryl ring system, each of the monocyclic or bicyclic ringsystems having 1-4 of the same or different heteroatoms selected fromthe group consisting of N, O and S wherein any of the above R₈ can beoptionally substituted by one or more R_(j);

[0036] R_(j) is selected from the group consisting of alkyl, cycloalkyl,aryl, heterocyclyl, heteroaryl, arylalkyl, alkoxy, aryloxy, alkanoyl,aroyl, arylalkoxy, alkoxycarbonyl, aryloxycarbonyl, alkanoyloxy,aroyloxy, carbamoyl wherein the nitrogen atom may be independently monoor di-substituted by alkyl, aryl, heterocyclyl or heteroaryl,alkanoylamino, aroylamino, alkylthio wherein the sulfur atom may beoxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom maybe oxidized to a sulfoxide or sulfone, arylalkylthio wherein the sulfuratom may be oxidized to a sulfoxide or sulfone, ureido wherein eithernitrogen atom may be independently substituted by alkyl, aryl,heterocyclyl or heteroaryl; alkoxycarbonylamino, aryloxycarbonylamino,alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino,arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino whereinthe nitrogen atom may be independently mono or di-substituted by alkyl,aryl, heterocyclyl or heteroaryl; halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino, R_(j) may be further optionallysubstituted by one or more R_(k);

[0037] R_(k) is selected from the group consisting of alkyl, cycloalkyl,aryl, heterocyclyl, heteroaryl, alkoxy, aryloxy, arylalkoxy,alkoxycarbonyl, aryloxycarbonyl, alkanoyloxy, aroyloxy, carbamoylwherein the nitrogen atom may be independently mono or di-substituted byalkyl, aryl, heterocyclyl or heteroaryl, alkanoylamino, aroylamino,alkylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, arylthio wherein the sulfur atom may be oxidized to a sulfoxideor sulfone, ureido wherein either nitrogen atom may be independentlysubstituted by alkyl, aryl, heterocyclyl or heteroaryl,alkoxycarbonylamino, aryloxycarbonylamino, arylalkoxycarbonylamino,arylalkoxycarbonylaminoalkyl, alkylcarbamoyloxy, arylcarbamoyloxy,alkylsulfonylamino, arylsulfonylamino, alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom may be independentlymono or di-substituted by alkyl, aryl, heterocyclyl or heteroaryl,halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino;

[0038] X is O, S or N—OH;

[0039] and the pharmacurtically acceptable derivatives thereof;

[0040] with the proviso that when R₆ is alkyl the alkyl must besubstituted with R_(f) wherein R_(f) is not hydroxy, sulfhydryl orhalogen.

[0041] Preferred compounds of the formula (I) are those wherein:

[0042] R_(a) is selected from the group consisting of H, alkyl and aryl;

[0043] R₁ is C1-8 alkyl, C3-7 cycloalkyl, aryl, heterocyclyl selectedfrom the group consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, pyranyl, thiopyranyl, piperazinyl and indolinyl;heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, or amino wherein R1 isoptionally substituted by one or more R_(b);

[0044] R_(b) is selected from the group consisting of C1-8 alkyl, C3-7cycloalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, C1-8 alkoxy, aryloxy, C1-8alkoxycarbonyl, aryloxycarbonyl, C1-8 alkanoyloxy, aroyloxy, carbamoylwherein the nitrogen atom may be independently mono or di-substituted byC1-8 alkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl, or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, C1-8 alkanoylamino,aroylamino, C1-8 alkylthio wherein the sulfur atom may be oxidized to asulfoxide or sulfone, arylthio wherein the sulfur atom may be oxidizedto a sulfoxide or sulfone, ureido wherein either nitrogen atom may beindependently substituted by alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl, or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, alkoxycarbonylamino, aryloxycarbonylamino, C1-8alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino,arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino whereinthe nitrogen atom may be independently mono or di-substituted by alkyl,aryl, heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl,oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyridinyl,pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl and phenoxazinyl, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino, R_(b) may be further optionallysubstituted by one or more R_(c);

[0045] R_(c) is selected from the group consisting of C1-8 alkyl, C3-6cycloalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, C1-8 alkoxy, aryloxy,halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino;

[0046] R₃ is H, C1-8 alkyl, C3-7 cycloalkyl or aryl wherein R₃ isoptionally substituted by one or more R_(d);

[0047] R_(d) is selected from the group consisting of C1-8 alkyl, C3-7cycloalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, C1-8 alkoxy, aryloxy,alkanoyl, aroyl, C1-8 alkoxycarbonyl, aryloxycarbonyl, C1-8 alkanoyloxy,aroyloxy, carbamoyl wherein the nitrogen atom may be independently monoor di-substituted by C1-8 alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl, or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, C1-8 alkanoylamino, aroylamino, C1-8 alkylthio whereinthe sulfur atom may be oxidized to a sulfoxide or sulfone, arylthiowherein the sulfur atom may be oxidized to a sulfoxide or sulfone,ureido wherein either nitrogen atom may be independently substituted byalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, alkoxycarbonylamino,aryloxycarbonylamino, C1-8 alkylcarbamoyloxy, arylcarbamoyloxy,alkylsulfonylamino, arylsulfonylamino, alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom may be independentlymono or di-substituted by alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidinoand guanidino, R_(d) may be further optionally substituted by one ormore R_(e);

[0048] R_(e) is selected from the group consisting of C1-8 alkyl, C3-6cycloalkyl, aryl, arylalkyl, C1-8 alkoxy, aryloxy, arylalkoxy, aroyl,amino, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino andguanidino;

[0049] R₅ is H or alkyl;

[0050] R₆ is H, C1-8 alkyl, C3-7 cycloalkyl or aryl wherein R₆ isoptionally substituted by one or more R_(f);

[0051] R_(f) is selected from the group consisting of C1-8 alkyl, C3-7cycloalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, C1-8 alkoxy, aryloxy,arylC1-8alkoxy, heteroarylC1-8alkoxy, C1-8 alkoxycarbonyl,aryloxycarbonyl, C1-8 alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom may be independently mono or di-substituted by C1-8 alkyl,aryl, heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl,oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyridinyl,pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl and phenoxazinyl, C1-8 alkanoylamino, aroylamino, C1-8alkylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, arylthio wherein the sulfur atom may be oxidized to a sulfoxideor sulfone, arylC1-8 alkylthio wherein the sulfur atom may be oxidizedto a sulfoxide or sulfone, ureido wherein either nitrogen atom may beindependently substituted by alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, alkoxycarbonylamino, aryloxycarbonylamino, C1-8alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino,arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino whereinthe nitrogen atom may be independently mono or di-substituted by alkyl,aryl, heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl,oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyridinyl,pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl and phenoxazinyl, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino, R_(f) may be further optionallysubstituted by one or more R_(g);

[0052] R_(g) is selected from the group consisting of C1-8 alkyl, C3-7cycloalkyl, aryl optionally substituted by halogen, C1-3alkyl orC1-3alkoxy; heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, C1-8 alkoxy, aryloxy,arylC1-8alkoxy, C1-8 alkoxycarbonyl, aryloxycarbonyl, C1-8 alkanoyloxy,aroyloxy, carbamoyl wherein the nitrogen atom may be independently monoor di-substituted by C1-8 alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl, or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, C1-8 alkanoylamino, aroylamino, C1-8 alkylthio whereinthe sulfur atom may be oxidized to a sulfoxide or sulfone, arylthiowherein the sulfur atom may be oxidized to a sulfoxide or sulfone,ureido wherein either nitrogen atom may be independently substituted byalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl, or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl or phenoxazinyl, alkoxycarbonylamino,aryloxycarbonylamino, C1-8 alkylcarbamoyloxy, arylcarbamoyloxy,alkylsulfonylamino, arylsulfonylamino, alkylaminosulfonyl andarylaminosulfonyl, amino wherein the nitrogen atom may be independentlymono or di-substituted by alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl, or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidinoand guanidino;

[0053] R_(h) is selected from the group consisting of C1-8 alkyl, aryl,C1-8 alkoxycarbonyl, aryloxycarbonyl, arylC1-8alkoxycarbonyl, carbamoylwherein the nitrogen atom may be optionally mono or di-substituted witha group selected from C1-8 alkyl, C3-7 cycloalkyl, aryl, arylC1-8alkyl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl,oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyridinyl,pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl and phenoxazinyl, halogen, hydroxy, carboxy and cyano;

[0054] R₈ is a heteroaryl ring selected from the group consisting offuranyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl,isoxazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl,triazinyl, indolizinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,indazolyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, triazolyl,tetrazolyl, purinyl, quinolizinyl, quinolinyl, isoquinolinyl,cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, naphthyridinyl,pteridinyl, carbazolyl, acridinyl and phenazinyl, wherein any of theabove R₈ can be optionally substituted by one or more R_(j);

[0055] R_(j) is selected from the group consisting of alkyl, cycloalkyl,aryl, heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl;heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl,oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyridinyl,pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl and phenoxazinyl, arylalkyl, alkoxy, aryloxy, arylalkoxy,alkoxycarbonyl, aryloxycarbonyl, alkanoyloxy, aroyloxy, carbamoylwherein the nitrogen atom may be independently mono or di-substituted byalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl, or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, alkanoylamino, aroylamino,alkylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, arylthio wherein the sulfur atom may be oxidized to a sulfoxideor sulfone, arylalkylthio wherein the sulfur atom may be oxidized to asulfoxide or sulfone, ureido wherein either nitrogen atom may beindependently substituted by alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, alkoxycarbonylamino, aryloxycarbonylamino, C1-8alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino,arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino whereinthe nitrogen atom may be independently mono or di-substituted by alkyl,aryl, heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl,oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyridinyl,pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl and phenoxazinyl, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino, R_(j) may be further optionallysubstituted by one or more R_(k);

[0056] R_(k) is selected from the group consisting of alkyl, cycloalkyl,aryl, heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl;heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl,oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyridinyl,pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl and phenoxazinyl, alkoxy, aryloxy, arylalkoxy,alkoxycarbonyl, aryloxycarbonyl, alkanoyloxy, aroyloxy, carbamoylwherein the nitrogen atom may be independently mono or di-substituted byalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, alkanoylamino, aroylamino,alkylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, arylthio wherein the sulfur atom may be oxidized to a sulfoxideor sulfone, ureido wherein either nitrogen atom may be independentlysubstituted by alkyl, aryl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, alkoxycarbonylamino, aryloxycarbonylamino,arylalkoxycarbonylamino, arylalkoxycarbonylaminoalkyl, C1-8alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino,arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino whereinthe nitrogen atom may be independently mono or di-substituted by alkyl,aryl, heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl,oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyridinyl,pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl and phenoxazinyl, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino;

[0057] X is O or S.

[0058] More preferred compounds of the formula (I) are those wherein:

[0059] Y is O or S;

[0060] R₁ is C1-5 alkyl, C3-7 cycloalkyl, phenyl, naphthyl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, pyranyl, thiopyranyl, piperazinyl andindolinyl, heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl,tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl,isoquinolinyl, quinazolinyl and quinoxalinyl or amino wherein R1 isoptionally substituted by one or more R_(b);

[0061] R_(b) is selected from the group consisting of C1-5 alkyl, C3-7cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl, heteroaryl selected from the group consistingof furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl,triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,quinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl, C1-5 alkoxy,aryloxy, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy,aroyloxy, carbamoyl wherein the nitrogen atom may be independently monoor di-substituted by C1-8 alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, quinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl,C1-5 alkanoylamino, aroylamino, C1-5 alkylthio wherein the sulfur atommay be oxidized to a sulfoxide or sulfone, arylthio wherein the sulfuratom may be oxidized to a sulfoxide or sulfone, ureido wherein eithernitrogen atom may be independently substituted by alkyl, aryl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl,pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, C1-5 alkoxycarbonylamino,aryloxycarbonylamino, C1-5 alkylcarbamoyloxy, arylcarbamoyloxy, C1-5alkylsulfonylamino, arylsulfonylamino, C1-5 alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom may be independentlymono or di-substituted by alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, quinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl,halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino,R_(b) may be further optionally substituted by one or more R_(c);

[0062] R_(c) is selected from the group consisting of C1-5 alkyl, C3-6cycloalkyl, aryl, heterocyclyl selected from the group consisting ofpiperidinyl, morpholinyl and piperazinyl; heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, tetrazolyl and pyridinyl, C1-5 alkoxy, aryloxy, halogen,hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino;

[0063] R₂ is H or C1-3 alkyl;

[0064] R₃ is H, C1-5 alkyl, C3-7 cycloalkyl or aryl, wherein R₃ isoptionally substituted by one or more R_(d);

[0065] R_(d) is selected from the group consisting of C1-5 alkyl, C3-7cycloalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl,tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl,isoquinolinyl, quinazolinyl and quinoxalinyl, C1-5 alkoxy, aryloxy,C1-5alkanoyl, aroyl, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom may beindependently mono or di-substituted by C1-5 alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl,pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, C1-5 alkanoylamino, aroylamino, C1-5alkylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, arylthio wherein the sulfur atom may be oxidized to a sulfoxideor sulfone, ureido wherein either nitrogen atom may be independentlysubstituted by C1-5 alkyl, aryl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl or heteroaryl selected the group consisting offuranyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl,tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl,isoquinolinyl, quinazolinyl and quinoxalinyl, C1-5 alkoxycarbonylamino,aryloxycarbonylamino, C1-5 alkylcarbamoyloxy, arylcarbamoyloxy, C1-5alkylsulfonylamino, arylsulfonylamino, C1-5 alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom may be independentlymono or di-substituted by C1-5 alkyl, aryl, heterocyclyl selected fromthe group consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, quinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl,halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino,R_(d) may be further optionally substituted by one or more R_(e);

[0066] R_(e) is selected from the group consisting of C1-5 alkyl, C3-6cycloalkyl, aryl, arylalkyl, C1-5 alkoxy, aryloxy, arylC1-5alkoxy,aroyl, amino, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino andguanidino;

[0067] R₄ is H or C1-3 alkyl;

[0068] R₅ is H or C1-8 alkyl;

[0069] R₆ is H, C1-5 alkyl, C3-7 cycloalkyl or aryl wherein R₆ isoptionally substituted by one or more R_(f);

[0070] R_(f) is selected from the group consisting of C1-5 alkyl, C3-7cycloalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl,tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl,isoquinolinyl, quinazolinyl and quinoxalinyl, C1-5 alkoxy, aryloxy,arylC1-5alkoxy, heteroarylC1-5alkoxy, C1-5 alkoxycarbonyl,aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom may be independently mono or di-substituted by C1-5 alkyl,aryl, heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl,pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, C1-5 alkanoylamino, aroylamino, C1-5alkylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, arylthio wherein the sulfur atom may be oxidized to a sulfoxideor sulfone, arylC1-5 alkylthio wherein the sulfur atom may be oxidizedto a sulfoxide or sulfone, ureido wherein either nitrogen atom may beindependently substituted by C1-5 alkyl, aryl, heterocyclyl selectedfrom the group consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, quinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl,C1-5 alkoxycarbonylamino, aryloxycarbonylamino, C1-5 alkylcarbamoyloxy,arylcarbamoyloxy, C1-5 alkylsulfonylamino, arylsulfonylamino, C1-5alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atommay be independently mono or di-substituted by C1-5 alkyl, aryl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl,pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino, R_(f) may be further optionallysubstituted by one or more R_(g);

[0071] R_(g) is selected from the group consisting of C1-5 alkyl, C3-7cycloalkyl, aryl optionally substituted by halogen, methyl or methoxy;heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl;heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl,pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, C1-5 alkoxy, aryloxy, arylC1-5alkoxy,C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy,carbamoyl wherein the nitrogen atom may be independently mono ordi-substituted by C1-5 alkyl, aryl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, quinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl,C1-5 alkanoylamino, aroylamino, C1-5 alkylthio wherein the sulfur atommay be oxidized to a sulfoxide or sulfone, arylthio wherein the sulfuratom may be oxidized to a sulfoxide or sulfone, ureido wherein eithernitrogen atom may be independently substituted by C1-5 alkyl, aryl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl,pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, C1-5 alkoxycarbonylamino,aryloxycarbonylamino, C1-5 alkylcarbamoyloxy, arylcarbamoyloxy, C1-5alkylsulfonylamino, arylsulfonylamino, C1-5 alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom may be independentlymono or di-substituted by C1-5 alkyl, aryl, heterocyclyl selected fromthe group consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, quinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl,halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino;

[0072] R_(h) is selected from the group consisting of C1-5 alkyl, aryl,C1-5 alkoxycarbonyl, aryloxycarbonyl, arylC1-5alkoxycarbonyl, carbamoylwherein the nitrogen atom may be optionally mono or di-substituted witha group selected from C1-5 alkyl, C3-7 cycloalkyl, aryl, arylC1-5alkyl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl,pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, halogen, hydroxy, carboxy and cyano;

[0073] R_(i) is alkoxy, aryloxy or hydroxy;

[0074] R₈ is a heteroaryl ring selected from the group consisting offuranyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl,isoxazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl,triazinyl, indolizinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,indazolyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl,quinolizinyl, quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl,quinazolinyl, quinoxalinyl, naphthyridinyl, pteridinyl, carbazolyl,acridinyl and phenazinyl, wherein any of the above R₈ can be optionallysubstituted by one or more R_(j);

[0075] R_(j) is selected from the group consisting of C1-8alkyl,C3-7cycloalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl; arylC1-8alkyl, C1-8alkoxy,aryloxy, arylC1-8alkoxy, C1-8alkoxycarbonyl, aryloxycarbonyl,C1-8alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom may beindependently mono or di-substituted by C1-8alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl,triazolyl, tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl,pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, C1-8alkanoylamino, aroylamino, C1-8alkylthio whereinthe sulfur atom may be oxidized to a sulfoxide or sulfone, arylthiowherein the sulfur atom may be oxidized to a sulfoxide or sulfone,arylC1-8alkylthio wherein the sulfur atom may be oxidized to a sulfoxideor sulfone, ureido wherein either nitrogen atom may be independentlysubstituted by C1-8 alkyl, aryl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl, or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, alkoxycarbonylamino, aryloxycarbonylamino, C1-8alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino,arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino whereinthe nitrogen atom may be independently mono or di-substituted by C1-8alkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl, or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, halogen, hydroxy, oxo,carboxy, cyano, nitro, amidino and guanidino, R_(j) may be furtheroptionally substituted by one or more R_(k);

[0076] R_(k) is selected from the group consisting of C1-8 alkyl, C3-7cycloalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl, heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, C1-8 alkoxy, aryloxy,arylC1-8alkoxy, C1-8alkoxycarbonyl, aryloxycarbonyl, C1-8alkanoyloxy,aroyloxy, carbamoyl wherein the nitrogen atom may be independently monoor di-substituted by C1-8alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl, or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, alkanoylamino, aroylamino, C1-8alkylthio wherein thesulfur atom may be oxidized to a sulfoxide or sulfone, arylthio whereinthe sulfur atom may be oxidized to a sulfoxide or sulfone, ureidowherein either nitrogen atom may be independently substituted byC1-8alkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, C1-8alkoxycarbonylamino,aryloxycarbonylamino, arylC1-8alkoxycarbonylamino,arylalkoxycarbonylaminoC1-8alkyl, C1-8 alkylcarbamoyloxy,arylcarbamoyloxy, C1-8alkylsulfonylamino, arylsulfonylamino,C1-8alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogenatom may be independently mono or di-substituted by C1-8alkyl, aryl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl,oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyridinyl,pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl and phenoxazinyl, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino.

[0077] Even more preferred compounds of the formula (I) are thosewherein:

[0078] Y is O;

[0079] R₁ is C1-5 alkyl, C3-7 cycloalkyl, phenyl, naphthyl, heterocyclylselected from the group consisting of piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl, pyranyl and thiopyranyl, heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyland isoquinolinyl, or amino wherein R₁ is optionally substituted by oneor more R_(b);

[0080] R_(b) is selected from the group consisting of C1-5 alkyl, C3-7cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl; heteroaryl selected from the group consistingof furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl,tetrazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl andisoquinolinyl; C1-5 alkoxy, aryloxy, C1-5 alkoxycarbonyl,aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom may be independently mono or di-substituted by C1-5 alkyl,phenyl, naphthyl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, piperazinyl and indolinyl, orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, tetrazolyl, pyridinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, quinolinyl and isoquinolinyl, C1-5 alkanoylamino,aroylamino, C1-5 alkylthio wherein the sulfur atom may be oxidized to asulfoxide or sulfone, arylthio wherein the sulfur atom may be oxidizedto a sulfoxide or sulfone, ureido wherein either nitrogen atom may beindependently substituted by alkyl or aryl; C1-5 alkoxycarbonylamino,aryloxycarbonylamino, C1-5 alkylcarbamoyloxy, arylcarbamoyloxy, C1-5alkylsulfonylamino, arylsulfonylamino, C1-5 alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom may be independentlymono or di-substituted by alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl andisoquinolinyl, halogen, hydroxy, oxo, carboxy, cyano and nitro, R_(b)may be further optionally substituted by one or more R_(c);

[0081] R_(c) is selected from the group consisting of C1-5 alkyl, C3-6cycloalkyl, aryl, C1-5 alkoxy, aryloxy, halogen, hydroxy, oxo, carboxy,and cyano;

[0082] R₂ is H or methyl;

[0083] R₃ is H, C1-5 alkyl, C3-7 cycloalkyl or phenyl, wherein R₃ isoptionally substituted by one or more R_(d);

[0084] R_(d) is selected from the group consisting of C1-3 alkyl, C3-6cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of piperidinyl, morpholinyl and piperazinyl; heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyland isoquinolinyl, C1-5 alkoxy, aryloxy, aroyl, C1-5 alkoxycarbonyl,aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom may be independently mono or di-substituted by C1-5 alkyl,aryl, heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl and piperazinyl or heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl andisoquinolinyl, C1-5 alkanoylamino, aroylamino, C1-5 alkylthio whereinthe sulfur atom may be oxidized to a sulfoxide or sulfone, arylthiowherein the sulfur atom may be oxidized to a sulfoxide or sulfone,ureido wherein either nitrogen atom may be independently substituted byC1-5 alkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of piperidinyl, morpholinyl and piperazinyl or heteroarylselected the group consisting of furanyl, thienyl, pyrrolyl, oxazolyl,thiazolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl andisoquinolinyl, C1-5 alkoxycarbonylamino, aryloxycarbonylamino, C1-5alkylcarbamoyloxy, arylcarbamoyloxy, C1-5 alkylsulfonylamino,arylsulfonylamino, C1-5 alkylaminosulfonyl, arylaminosulfonyl, aminowherein the nitrogen atom may be independently mono or di-substituted byC1-5 alkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of piperidinyl, morpholinyl and piperazinyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyland isoquinolinyl, halogen, hydroxy, oxo, carboxy and cyano, R_(d) maybe further optionally substituted by one or more R_(e);

[0085] R_(e) is selected from the group consisting of C1-5 alkyl, C3-6cycloalkyl, aryl, arylC1-5alkyl, C1-5 alkoxy, aryloxy, arylC1-3alkoxy,aroyl, amino, halogen, hydroxy, oxo, carboxy and cyano;

[0086] R₄ is H or methyl;

[0087] R₅ is H or C1-5 alkyl;

[0088] R₆ is H, C1-5 alkyl, C3-7 cycloalkyl, phenyl or naphthyl whereinR₆ is optionally substituted by one or more R_(f);

[0089] R_(f) is selected from the group consisting of C1-5 alkyl, C3-7cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl; heteroaryl selected from the group consistingof furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl,triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,quinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl, C1-5 alkoxy,aryloxy, arylC1-5alkoxy, pyridylC1-5alkoxy, thienylC1-5alkoxy,furanylC1-5alkoxy, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom may beindependently mono or di-substituted by C1-5 alkyl, aryl, heterocyclylselected from the group consisting of piperidinyl, morpholinyl andpiperazinyl or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,quinolinyl and isoquinolinyl, C1-5 alkanoylamino, aroylamino, C1-5alkylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, arylthio wherein the sulfur atom may be oxidized to a sulfoxideor sulfone, arylC1-5 alkylthio wherein the sulfur atom may be oxidizedto a sulfoxide or sulfone, ureido wherein either nitrogen atom may beindependently substituted by C1-5 alkyl, aryl, heterocyclyl selectedfrom the group consisting of piperidinyl, morpholinyl and piperazinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,quinolinyl and isoquinolinyl, C1-5 alkoxycarbonylamino,aryloxycarbonylamino, C1-5 alkylcarbamoyloxy, arylcarbamoyloxy, C1-5alkylsulfonylamino, arylsulfonylamino, C1-5 alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom may be independentlymono or di-substituted by C1-5 alkyl, aryl, heterocyclyl selected fromthe group consisting of pyrrolidinyl, piperidinyl, morpholinyl andpiperazinyl or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,quinolinyl and isoquinolinyl, halogen, hydroxy, oxo, carboxy and cyano,R_(f) may be further optionally substituted by one or more R_(g);

[0090] R_(g) is selected from the group consisting of C1-5 alkyl, C3-7cycloalkyl, phenyl optionally substituted by halogen, methyl or methoxy;naphthyl optionally substituted by halogen, methyl or methoxy;heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl;heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl,pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, C1-5 alkoxy, aryloxy, arylC1-5alkoxy,C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy,carbamoyl wherein the nitrogen atom may be independently mono ordi-substituted by C1-5 alkyl, aryl, heterocyclyl selected from the groupconsisting of piperidinyl, morpholinyl and piperazinyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyland isoquinolinyl, C1-5 alkanoylamino, aroylamino, C1-5 alkylthiowherein the sulfur atom may be oxidized to a sulfoxide or sulfone,arylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, ureido wherein either nitrogen atom may be independentlysubstituted by C1-5 alkyl, aryl, heterocyclyl selected from the groupconsisting of piperidinyl, morpholinyl and piperazinyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl,isoquinolinyl, C1-5 alkoxycarbonylamino, aryloxycarbonylamino, C1-5alkylcarbamoyloxy, arylcarbamoyloxy, C1-5 alkylsulfonylamino,arylsulfonylamino, C1-5 alkylaminosulfonyl, arylaminosulfonyl, aminowherein the nitrogen atom may be independently mono or di-substituted byC1-5 alkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl and piperazinyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyland isoquinolinyl, halogen, hydroxy, oxo, carboxy and cyano;

[0091] R_(h) is selected from the group consisting of C1-5 alkyl,phenyl, naphthyl, C1-5 alkoxycarbonyl, aryloxycarbonyl,arylC1-3alkoxycarbonyl, carbamoyl wherein the nitrogen atom may beoptionally mono or di-substituted with a group selected from C1-5 alkyl,C3-6 cycloalkyl, phenyl, naphthyl, arylC1-3alkyl, heterocyclyl selectedfrom the group consisting of pyrrolidinyl, piperidinyl, morpholinyl andpiperazinyl or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,quinolinyl and isoquinolinyl, halogen, hydroxy, carboxy and cyano;

[0092] Z is O or S;

[0093] R₈ is a heteroaryl ring selected from the group consisting offuranyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl,isoxazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl,triazinyl, indolizinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,indazolyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl,quinolizinyl, quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl,quinazolinyl, quinoxalinyl, naphthyridinyl, pteridinyl, carbazolyl,acridinyl and phenazinyl, wherein any of the above R₈ can be optionallysubstituted by one or more groups of the formula R_(j);

[0094] R_(j) is selected from the group consisting of C1-5alkyl,C3-6cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of piperidinyl, morpholinyl and piperazinyl; heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, tetrazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,quinolinyl and isoquinolinyl, arylC1-5alkyl, C1-5alkoxy, aryloxy,arylC1-5alkoxy, C1-5alkoxycarbonyl, aryloxycarbonyl, C1-5alkanoyloxy,aroyloxy, carbamoyl wherein the nitrogen atom may be independently monoor di-substituted by C1-5alkyl, aryl, heterocyclyl selected from thegroup consisting of piperidinyl, morpholinyl and piperazinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, tetrazolyl, pyridinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, quinolinyl and isoquinolinyl, C1-5alkanoylamino,aroylamino, C1-5alkylthio wherein the sulfur atom may be oxidized to asulfoxide or sulfone, arylthio wherein the sulfur atom may be oxidizedto a sulfoxide or sulfone, arylC1-5alkylthio wherein the sulfur atom maybe oxidized to a sulfoxide or sulfone, ureido wherein either nitrogenatom may be independently substituted by C1-5 alkyl, aryl, heterocyclylselected from the group consisting of piperidinyl, morpholinyl andpiperazinyl or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, tetrazolyl,pyridinyl, indolyl, benzofuranyl, benzothienyl, benzimidazolyl,benzthiazolyl, benzoxazolyl, quinolinyl and isoquinolinyl,C1-5alkoxycarbonylamino, aryloxycarbonylamino, C1-5 alkylcarbamoyloxy,arylcarbamoyloxy, C1-5 alkylsulfonylamino, arylsulfonylamino,C1-5alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogenatom may be independently mono or di-substituted by C1-5 alkyl, aryl,heterocyclyl selected from the group consisting of piperidinyl,morpholinyl and piperazinyl or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, tetrazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl andisoquinolinyl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino andguanidino, R_(j) may be further optionally substituted by one or moreR_(k);

[0095] R_(k) is selected from the group consisting of C1-3 alkyl, C3-6cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of piperidinyl, morpholinyl and piperazinyl; heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,tetrazolyl and pyridinyl, C1-3 alkoxy, aryloxy, arylC1-3alkoxy,C1-3alkoxycarbonyl, aryloxycarbonyl, C1-3alkanoyloxy, aroyloxy,carbamoyl wherein the nitrogen atom may be independently mono ordi-substituted by C1-3 alkyl, aryl, heterocyclyl selected from the groupconsisting of morpholinyl and piperazinyl or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, tetrazolyl, and pyridinyl, C1-3alkanoylamino, aroylamino,C1-3alkylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, arylthio wherein the sulfur atom may be oxidized to a sulfoxideor sulfone, ureido wherein either nitrogen atom may be independentlysubstituted by C1-3alkyl, phenyl, naphthyl or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, tetrazolyl and pyridinyl, C1-3alkoxycarbonylamino,aryloxycarbonylamino, arylC1-3alkoxycarbonylamino,benzyloxycarbonylaminoC1-5alkyl, C1-3 alkylcarbamoyloxy,arylcarbamoyloxy, C1-3 alkylsulfonylamino, arylsulfonylamino,C1-3alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogenatom may be independently mono or di-substituted by C1-3alkyl, aryl,heterocyclyl selected from the group consisting of piperidinyl,morpholinyl and piperazinyl or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, tetrazolylpyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl andisoquinolinyl, halogen, hydroxy, oxo, carboxy, cyano and nitro; and

[0096] X is O.

[0097] Yet even more preferred compounds of the formula (I) are thosewherein:

[0098] R₁ is C1-5 alkyl, C3-6 cycloalkyl, phenyl, naphthyl, heterocyclylselected from the group consisting of piperidinyl, morpholinyl,piperazinyl, pyranyl and thiopyranyl; heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl andisoquinolinyl, or amino, wherein R₁ is optionally substituted by one ormore R_(b);

[0099] R_(b) is selected from the group consisting of C1-3 alkyl, C3-6cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl and piperazinyl,heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, tetrazolyl, pyridinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, quinolinyl and isoquinolinyl, C1-3 alkoxy, phenoxy, C1-3alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoylwherein the nitrogen atom may be independently mono or di-substituted byC1-5 alkyl, phenyl or heteroaryl selected from the group consisting offuranyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, quinolinyl and isoquinolinyl, C1-5 alkanoylamino,aroylamino, C1-5 alkylthio wherein the sulfur atom may be oxidized to asulfoxide or sulfone, arylthio wherein the sulfur atom may be oxidizedto a sulfoxide or sulfone, ureido wherein either nitrogen atom may beindependently substituted by C1-5alkyl, phenyl or naphthyl; C1-5alkoxycarbonylamino, C1-5 alkylcarbamoyloxy, arylcarbamoyloxy, C1-5alkylsulfonylamino, arylsulfonylamino, C1-5 alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom may be independentlymono or di-substituted by C1-5alkyl, phenyl, naphthyl, heterocyclylselected from the group consisting of piperidinyl, morpholinyl andpiperazinyl or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,quinolinyl and isoquinolinyl, halogen, hydroxy, oxo, carboxy and cyano,R_(b) may be further optionally substituted by one or more R_(c);

[0100] R_(c) is selected from the group consisting of C1-3 alkyl, C5-6cycloalkyl, aryl, C1-3 alkoxy, phenoxy, halogen, hydroxy, oxo, carboxyand cyano;

[0101] R₂ is H;

[0102] R₃ is C1-5 alkyl, C3-6 cycloalkyl or phenyl, wherein R₃ isoptionally substituted by one or more R_(d);

[0103] R_(d) is selected from the group consisting of C1-3 alkyl, C3-6cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of piperidinyl, morpholinyl and piperazinyl; heteroarylselected from the group consisting of furanyl, thienyl, thiazolyl,imidazolyl, pyridinyl, indolyl, quinolinyl and isoquinolinyl, C1-5alkoxy, phenoxy, aroyl, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom may beindependently mono or di-substituted by C1-5 alkyl, phenyl, naphthyl,heterocyclyl selected from the group consisting of piperidinyl,morpholinyl and piperazinyl or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl and indolyl, C1-5 alkanoylamino, aroylamino, C1-3alkylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, phenylthio wherein the sulfur atom may be oxidized to asulfoxide or sulfone, ureido wherein either nitrogen atom may beindependently substituted by C1-3 alkyl, phenyl or heteroaryl selectedthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl and indolyl, C1-5 alkoxycarbonylamino, C1-5alkylcarbamoyloxy, arylcarbamoyloxy, C1-5 alkylsulfonylamino,arylsulfonylamino, amino wherein the nitrogen atom may be independentlymono or di-substituted by C1-3 alkyl, phenyl, heterocyclyl selected fromthe group consisting of piperidinyl, morpholinyl and piperazinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl and indolyl,halogen, hydroxy, oxo, carboxy and cyano, R_(d) may be furtheroptionally substituted by one or more R_(e);

[0104] R_(e) is selected from the group consisting of C1-5 alkyl, C5-6cycloalkyl, phenyl, naphthyl, arylC1-3alkyl, C1-5 alkoxy, phenoxy,arylC1-3alkoxy, aroyl, amino, halogen, hydroxy, oxo, carboxy and cyano;

[0105] wherein the configuration at the stereocenter defined by R₂ andR₃ and the carbon they are attached to is L;

[0106] R₄ is H;

[0107] R₅ is H or C1-3 alkyl;

[0108] R₆ is H, C1-5 alkyl, C3-6 cycloalkyl or phenyl. wherein R₆ isoptionally substituted by one or more R_(f);

[0109] R_(f) is selected from the group consisting of C1-3 alkyl, C3-6cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl and piperazinyl;heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,quinolinyl and isoquinolinyl, C1-5 alkoxy, aryloxy, arylC1-3alkoxy,pyridylC1-5alkoxy, thienylC1-5alkoxy, furanylC1-5alkoxy, C1-5alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoylwherein the nitrogen atom may be independently mono or di-substituted byC1-5 alkyl, phenyl or heteroaryl selected from the group consisting offuranyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyland indolyl, C1-5 alkanoylamino, aroylamino, C1-3 alkylthio wherein thesulfur atom may be oxidized to a sulfoxide or sulfone, arylthio whereinthe sulfur atom may be oxidized to a sulfoxide or sulfone,arylC1-3alkylthio wherein the sulfur atom may be oxidized to a sulfoxideor sulfone, ureido wherein either nitrogen atom may be independentlysubstituted by C1-5 alkyl or phenyl; C1-5 alkoxycarbonylamino, C1-5alkylsulfonylamino, arylsulfonylamino, amino wherein the nitrogen atommay be independently mono or di-substituted by C1-5 alkyl, phenyl,naphthyl, heterocyclyl selected from the group consisting ofpiperidinyl, morpholinyl and piperazinyl or heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl and indolyl, halogen, hydroxy, oxo, carboxy andcyano, R_(f) may be further optionally substituted by one or more R_(g);

[0110] R_(g) is selected from the group consisting of C1-3 alkyl, C5-6cycloalkyl, phenyl optionally substituted by halogen, methyl or methoxy;heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl and piperazinyl; heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, pyrimidinyl, pyrazinyl and indolyl, C1-5 alkoxy,aryloxy, arylC1-3alkoxy, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom may beindependently mono or di-substituted by C1-5 alkyl or aryl; C1-5alkanoylamino, aroylamino, C1-5 alkylthio wherein the sulfur atom may beoxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom maybe oxidized to a sulfoxide or sulfone, ureido wherein either nitrogenatom may be independently substituted by C1-5 alkyl or aryl; C1-5alkoxycarbonylamino, aryloxycarbonylamino, C1-5 alkylcarbamoyloxy,arylcarbamoyloxy, C1-5 alkylsulfonylamino, arylsulfonylamino, C1-5alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atommay be independently mono or di-substituted by C1-5 alkyl or aryl;halogen, hydroxy, oxo, carboxy and cyano;

[0111] R_(h) is selected from the group consisting of C1-5 alkyl,phenyl, C1-5 alkoxycarbonyl, aryloxycarbonyl, arylC1-3alkoxycarbonyl,carbamoyl wherein the nitrogen atom may be optionally mono ordi-substituted with C1-5 alkyl, C3-6 cycloalkyl, phenyl, naphthyl,arylC1-3alkyl, halogen, hydroxy, carboxy and cyano;

[0112] wherein Z is O;

[0113] R₈ is a heteroaryl ring selected from the group consisting ofoxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl,pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl,isoquinolinyl, quinazolinyl and quinoxalinyl, wherein any of the aboveR₈ can be optionally substituted by one or more R_(j);

[0114] R_(j) is selected from the group consisting of C1-3 alkyl, C5-6cycloalkyl, phenyl, naphthyl, morpholinyl, piperazinyl, furanyl,thienyl, pyrrolyl, tetrazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,arylC1-3alkyl, C1-3alkoxy, aryloxy, arylC1-3alkoxy, C1-3alkoxycarbonyl,aryloxycarbonyl, C1-3alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom may be independently mono or di-substituted by C1-3alkyl,phenyl, naphthyl, piperidinyl, furanyl, thienyl, pyrrolyl, oxazolyl,thiazolyl, imidazolyl, tetrazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl orisoquinolinyl; C1-3alkanoylamino, aroylamino, C1-3alkylthio wherein thesulfur atom may be oxidized to a sulfoxide or sulfone, arylthio whereinthe sulfur atom may be oxidized to a sulfoxide or sulfone, arylC1-3alkylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, ureido wherein either nitrogen atom may be independentlysubstituted by C1-3 alkyl, phenyl, naphthyl, piperidinyl, morpholinyl,thiazolyl, imidazolyl, tetrazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl orisoquinolinyl; C1-3 alkoxycarbonylamino, aryloxycarbonylamino, C1-3alkylcarbamoyloxy, arylcarbamoyloxy, C1-3alkylsulfonylamino,arylsulfonylamino, C1-3alkylaminosulfonyl, arylaminosulfonyl, aminowherein the nitrogen atom may be independently mono or di-substituted byC1-3 alkyl, phenyl, naphthyl, piperidinyl, furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, tetrazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,quinolinyl or isoquinolinyl; halogen, hydroxy, oxo, carboxy, cyano andnitro, R_(j) may be further optionally substituted by one or more R_(k);

[0115] R_(k) is selected from the group consisting of methyl, C5-6cycloalkyl, phenyl, morpholinyl, furanyl, thienyl, pyrrolyl, tetrazolyl,pyridinyl, methoxy, phenoxy, benzyloxy, methoxycarbonyl, acetyloxy,benzoyloxy, carbamoyl wherein the nitrogen atom may be independentlymono or di-substituted by C1-3 alkyl, phenyl, furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl or pyridinyl; acetylamino,benzoylamino, methylthio wherein the sulfur atom may be oxidized to asulfoxide or sulfone, ureido wherein either nitrogen atom may beindependently substituted by methyl, phenyl, furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl or pyridinyl; arylC1-3alkoxycarbonylamino, benzyloxycarbonylaminoC1-5alkyl, amino wherein thenitrogen atom may be independently mono or di-substituted by C1-3alkyl,phenyl, naphthyl, furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl orisoquinolinyl, halogen, hydroxy, oxo, carboxy, cyano and nitro.

[0116] Still yet even more preferred compounds of the formula (I) arethose wherein:

[0117] R₁ is C1-3 alkyl, C5-6 cycloalkyl, phenyl, naphthyl, heterocyclylselected from the group consisting of piperidinyl, morpholinyl,piperazinyl, pyranyl and thiopyranyl; heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl and indolyl, or amino, wherein R1 is optionallysubstituted by one or more R_(b);

[0118] R_(b) is selected from the group consisting of C1-3 alkyl, C5-6cycloalkyl, phenyl, heterocyclyl selected from the group consisting ofpiperidinyl, morpholinyl and piperazinyl; heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, imidazolyl, tetrazolyl,pyridinyl, indolyl, benzofuranyl, benzothienyl, benzimidazolyl,benzthiazolyl, benzoxazolyl, quinolinyl and isoquinolinyl, C1-3 alkoxy,C1-3 alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy,carbamoyl wherein the nitrogen atom may be independently mono ordi-substituted by C1-3 alkyl, phenyl or heteroaryl selected from thegroup consisting of pyrrolyl, imidazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl and benzthiazolyl; C1-5alkanoylamino, aroylamino, C1-3 alkylthio wherein the sulfur atom may beoxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom maybe oxidized to a sulfoxide or sulfone, ureido wherein either nitrogenatom may be independently substituted by C1-3 alkyl or phenyl; C1-5alkylsulfonylamino, arylsulfonylamino, amino wherein the nitrogen atommay be independently mono or di-substituted by C1-3alkyl, phenyl,heterocyclyl selected from the group consisting of piperidinyl,morpholinyl and piperazinyl or heteroaryl selected from the groupconsisting of pyrrolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyland isoquinolinyl; halogen, hydroxy, oxo, carboxy and cyano, R_(b) maybe further optionally substituted by one or more R_(c);

[0119] R_(c) is selected from the group consisting of C1-3 alkyl, C5-6cycloalkyl, C1-3 alkoxy, halogen and hydroxy;

[0120] R₃ is C1-5 alkyl, C5-6 cycloalkyl or phenyl wherein R₃ isoptionally substituted by one or more R_(d);

[0121] R_(d) is selected from the group consisting of C1-3 alkyl, C3-6cycloalkyl, phenyl, naphthyl, 4-piperidinyl, 4-morpholinyl, piperazinyl,furanyl, thienyl, thiazolyl, imidazolyl, pyridinyl, indolyl, C1-5alkoxy, phenoxy, aroyl, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom may beindependently mono or di-substituted by C1-5 alkyl or phenyl; C1-5alkanoylamino, C1-3 alkylthio wherein the sulfur atom may be oxidized toa sulfoxide or sulfone, ureido wherein either nitrogen atom may beindependently substituted by C1-3 alkyl or phenyl; C1-5alkoxycarbonylamino, C1-5 alkylsulfonylamino, arylsulfonylamino, aminowherein the nitrogen atom may be independently mono or di-substituted byC1-3 alkyl or phenyl; halogen, hydroxy, oxo, carboxy and cyano, R_(d)may be further optionally substituted by one or more R_(e);

[0122] R_(e) is selected from the group consisting of C1-5 alkyl, C5-6cycloalkyl, phenyl, benzyl, C1-5 alkoxy, phenoxy, benzyloxy, aroyl,halogen, hydroxy, oxo, carboxy and cyano;

[0123] R₆ is H, C1-5 alkyl or phenyl wherein R₆ is optionallysubstituted by one or more R_(f);

[0124] R_(f) is selected from the group consisting of C1-3 alkyl, C3-6cycloalkyl, phenyl, naphthyl, furanyl, thienyl, thiazolyl, imidazolyl,pyridinyl, indolyl, C1-3 alkoxy, benzyloxy, pyridyl, C1-3alkoxy,thienylC1-3alkoxy, furanylC1-3alkoxy, C1-3 alkoxycarbonyl,phenoxyoxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom may be independently mono or di-substituted by C1-3 alkylor phenyl; C1-5 alkanoylamino, aroylamino, methylthio wherein the sulfuratom may be oxidized to a sulfoxide or sulfone, benzylthio wherein thesulfur atom may be oxidized to a sulfoxide or sulfone, ureido whereineither nitrogen atom may be independently substituted by C1-5 alkyl orphenyl; C1-3 alkoxycarbonylamino, amino wherein the nitrogen atom may beindependently mono or di-substituted by C1-5 alkyl or phenyl; halogen,hydroxy, oxo, carboxy and cyano, R_(f) may be further optionallysubstituted by one or more R_(g);

[0125] R_(g) is selected from the group consisting of C1-3 alkyl, phenyloptionally substituted by halogen, methyl or methoxy; heterocyclylselected from the group consisting of piperidinyl, morpholinyl andpiperazinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl and pyridinyl, C1-3 alkoxy, aryloxy, benzyloxy, C1-5alkoxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom may be independently mono or di-substituted by C1-5 alkylor phenyl; C1-5 alkanoylamino, aroylamino, C1-5 alkylthio wherein thesulfur atom may be oxidized to a sulfoxide or sulfone, ureido whereineither nitrogen atom may be independently substituted by C1-5 alkyl orphenyl; C1-5 alkoxycarbonylamino, C1-5 alkylcarbamoyloxy,arylcarbamoyloxy, C1-3 alkylsulfonylamino, arylsulfonylamino, C1-3alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atommay be independently mono or di-substituted by C1-3 alkyl or phenyl;halogen, hydroxy, oxo, carboxy and cyano;

[0126] R_(h) is selected from the group consisting of C1-3 alkyl,phenyl, C1-3 alkoxycarbonyl, phenoxyoxycarbonyl, benzyloxy, carbamoylwherein the nitrogen atom may be optionally mono or di-substituted withC1-5 alkyl, phenyl, benzyl, halogen, hydroxy, carboxy and cyano;

[0127] R₈ is a heteroaryl ring selected from the group consisting ofoxazolyl, thiazolyl, imidazolyl, pyridyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyland isoquinolinyl, wherein any of the above R₈ can be optionallysubstituted by one or more R_(j);

[0128] R_(j) is selected from the group consisting of C1-3 alkyl, C5-6cycloalkyl, phenyl, naphthyl, morpholinyl, piperazinyl, furanyl,thienyl, pyrrolyl, tetrazolyl, pyridinyl, benzyl, C1-3alkoxy, phenoxy,benzyloxy, C1-3alkoxycarbonyl, acetyloxy, benzoyloxy, carbamoyl whereinthe nitrogen atom may be independently mono or di-substituted by methyl,phenyl, furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl orpyridinyl; acetylamino, benzoylamino, methylthio wherein the sulfur atommay be oxidized to a sulfoxide or sulfone, benzylthio wherein the sulfuratom may be oxidized to a sulfoxide or sulfone, ureido wherein eithernitrogen atom may be independently substituted by methyl, phenyl,thiazolyl, imidazolyl or pyridinyl; C1-3 alkoxycarbonylamino, C1-3alkylcarbamoyloxy, arylcarbamoyloxy, C1-3alkylsulfonylamino,arylsulfonylamino, amino wherein the nitrogen atom may be independentlymono or di-substituted by methyl, phenyl, furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl or pyridinyl; halogen, hydroxy, carboxy,cyano and nitro, R_(j) may be further optionally substituted by one ormore R_(k);

[0129] R_(k) is selected from the group consisting of methyl, C5-6cycloalkyl, phenyl, furanyl, thienyl, pyrrolyl, pyridinyl, methoxy,phenoxy, benzyloxy, methoxycarbonyl, acetyloxy, benzoyloxy, carbamoylwherein the nitrogen atom may be independently mono or di-substituted bymethyl, phenyl, furanyl or thienyl; acetylamino, benzoylamino,methylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, ureido wherein either nitrogen atom may be independentlysubstituted by methyl, phenyl, furanyl, thienyl, pyrrolyl, oxazolyl andthiazolyl, benzyloxycarbonylamino, benzyloxycarbonylaminoC1-5 alkyl,amino wherein the nitrogen atom may be independently mono ordi-substituted by C1-3alkyl, phenyl, furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl and pyridinyl, halogen, hydroxy,carboxy, cyano and nitro.

[0130] Even much more preferred compounds of the formula (I) are thosewherein:

[0131] R₁ is C5-6 cycloalkyl, phenyl, naphthyl, piperidinyl,morpholinyl, piperazinyl, furanyl, thienyl, pyrrolyl, pyranyl,thiopyranyl or amino wherein R₁ is optionally substituted by one or moreR_(b);

[0132] R_(b) is selected from the group consisting of C1-3 alkyl, C5-6cycloalkyl, phenyl, furanyl, thienyl, pyrrolyl, imidazolyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,C1-3 alkoxy, C1-3 alkoxycarbonyl, carbamoyl wherein the nitrogen atommay be independently mono or di-substituted by C1-3 alkyl or phenyl;C1-5 alkanoylamino, aroylamino, ureido wherein either nitrogen atom maybe independently substituted by C1-3alkyl or phenyl; C1-5alkylsulfonylamino, arylsulfonylamino, amino wherein the nitrogen atommay be independently mono or di-substituted by C1-3alkyl or phenyl;halogen, hydroxy, oxo, carboxy and cyano, R_(b) may be furtheroptionally substituted by one or more R_(c);

[0133] R_(c) is selected from the group consisting of C1-3 alkyl, C1-3alkoxy, halogen and hydroxy;

[0134] R_(d) is selected from the group consisting of C1-3 alkyl, C3-6cycloalkyl, phenyl, naphthyl, 4-piperidinyl, furanyl, thienyl,thiazolyl, imidazolyl, pyridinyl, indolyl, C1-3alkoxy,C1-5alkoxycarbonyl, C1-5alkanoyloxy, benzoyloxy, carbamoyl wherein thenitrogen atom may be independently mono or di-substituted by C1-3alkylor phenyl; C1-5alkanoylamino, C1-3 alkylthio wherein the sulfur atom maybe oxidized to a sulfoxide or sulfone, C1-3alkoxycarbonylamino,C1-3alkylsulfonylamino, amino wherein the nitrogen atom may beindependently mono or di-substituted by C1-3 alkyl or phenyl, halogen,hydroxy, oxo, carboxy and cyano, R_(d) may be further optionallysubstituted by one or more R_(e);

[0135] R_(e) is selected from the group consisting of C1-3 alkyl,phenyl, benzyl, C1-3 alkoxy, phenoxy, benzyloxy, benzoyl, halogen,hydroxy, oxo, carboxy and cyano;

[0136] R₅ is H or methyl;

[0137] R₆ is C1-5 alkyl or phenyl, wherein R₆ is optionally substitutedby one or more groups of the formula R_(f),

[0138] R_(f) is selected from the group consisting of methyl, C3-6cycloalkyl, phenyl, naphthyl, furanyl, thienyl, thiazolyl, imidazolyl,pyridinyl, indolyl, C1-3 alkoxy, benzyloxy, C1-5 alkanoylamino,aroylamino, methylthio wherein the sulfur atom may be oxidized to asulfoxide or sulfone, benzylthio wherein the sulfur atom may be oxidizedto a sulfoxide or sulfone, C1-3 alkoxycarbonylamino, amino wherein thenitrogen atom may be independently mono or di-substituted by C1-5 alkylor phenyl; halogen, hydroxy, oxo, carboxy and cyano, R_(f) may befurther optionally substituted by one or more R_(g);

[0139] R_(g) is selected from the group consisting of C1-3 alkyl, phenyloptionally substituted by halogen or methyl; C1-3 alkoxy, aryloxy,benzyloxy, C1-3 alkoxycarbonyl, carbamoyl wherein the nitrogen atom maybe independently mono or di-substituted by C1-3 alkyl or phenyl; C1-5alkanoylamino, aroylamino, amino wherein the nitrogen atom may beindependently mono or di-substituted by C1-3 alkyl or phenyl; halogen,hydroxy, oxo, carboxy and cyano;

[0140] R_(h) is selected from the group consisting of C1-3 alkyl,phenyl, C1-3 alkoxycarbonyl, benzyloxy and carboxy;

[0141] R₈ is a heteroaryl ring selected from the group consisting ofoxazolyl, thiazolyl, imidazolyl, pyridyl, benzimidazolyl, benzthiazolyland benzoxazolyl, wherein any of the above R₈ can be optionallysubstituted by one or more R_(j);

[0142] R_(j) is selected from the group consisting of methyl,cyclohexyl, phenyl, furanyl, thienyl, benzyl, methoxy, phenoxy,benzyloxy, methoxycarbonyl, acetyloxy, benzoyloxy, carbamoyl wherein thenitrogen atom may be independently mono or di-substituted by methyl,phenyl, furanyl or thienyl; acetylamino, benzoylamino, ureido whereineither nitrogen atom may be independently substituted by methyl orphenyl; methoxycarbonylamino, C1-3 alkylsulfonylamino,arylsulfonylamino, amino wherein the nitrogen atom may be independentlymono or di-substituted by methyl, phenyl, furanyl or thienyl; halogen,hydroxy, carboxy and cyano, R_(j) may be further optionally substitutedby one or more R_(k);

[0143] R_(k) is selected from the group consisting of methyl, phenyl,furanyl, thienyl, methoxy, phenoxy, benzyloxy, methoxycarbonyl,acetyloxy, benzoyloxy, carbamoyl wherein the nitrogen atom may beindependently mono or di-substituted by methyl or phenyl; acetylamino,benzoylamino, ureido wherein either nitrogen atom may be independentlysubstituted by methyl or phenyl; benzyloxycarbonylamino,benzyloxycarbonylaminoC1-3alkyl, amino wherein the nitrogen atom may beindependently mono or di-substituted by C1-3alkyl, phenyl, furanyl orthienyl; halogen, hydroxy, carboxy, cyano and nitro.

[0144] Yet even more preferred compounds of the formula (I) are thosewherein:

[0145] A is —C(O)— or —SO₂—;

[0146] R₁ is cyclohexyl, phenyl, naphthyl, piperidinyl, morpholinyl,piperazinyl, pyranyl, thiopyranyl or amino, wherein R1 is optionallysubstituted by one or more R_(b);

[0147] R_(b) is selected from the group consisting of C1-3 alkyl, C5-6cycloalkyl, phenyl, furanyl, thienyl, pyrrolyl, imidazolyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,C1-3 alkoxy, C1-3 alkoxycarbonyl, carbamoyl wherein the nitrogen atommay be independently mono or di-substituted by C1-3 alkyl or phenyl;C1-5 alkanoylamino, aroylamino, C1-5 alkylsulfonylamino,arylsulfonylamino, amino wherein the nitrogen atom may be independentlymono or di-substituted by C1-3 alkyl; halogen, hydroxy, oxo, carboxy andcyano, R_(b) may be further optionally substituted by one or more R_(c);

[0148] R_(c) is selected from the group consisting of C1-3 alkoxy,halogen and hydroxy;

[0149] R₃ is C1-5 alkyl or C5-6 cycloalkyl, wherein R₃ is optionallysubstituted by one or more R_(d);

[0150] R_(d) is selected from the group consisting of methyl, C3-6cycloalkyl, phenyl, thienyl, imidazolyl, pyridinyl, indolyl, C1-4alkoxy, C1-5 alkanoylamino, methylthio wherein the sulfur atom may beoxidized to a sulfoxide or sulfone, halogen, hydroxy, oxo, carboxy andcyano, R_(d) may be further optionally substituted by one or more R_(e);

[0151] R_(e) is selected from the group consisting of methyl, phenyl,benzyl, methoxy, phenoxy, benzyloxy, benzoyl, halogen and hydroxy;

[0152] R_(f) is selected from the group consisting of C3-6 cycloalkyl,phenyl, naphthyl, thienyl, imidazolyl, pyridinyl, indolyl, methoxy,benzyloxy, C1-3 alkanoylamino, methylthio wherein the sulfur atom may beoxidized to a sulfoxide or sulfone, benzylthio wherein the sulfur atommay be oxidized to a sulfoxide or sulfone, methoxycarbonylamino, aminowherein the nitrogen atom may be independently mono or di-substituted byC1-3 alkyl; halogen, hydroxy, carboxy and cyano, R_(f) may be furtheroptionally substituted by one or more R_(g);

[0153] R_(g) is selected from the group consisting of methyl, phenyloptionally substituted by halogen or methyl; methoxy, phenoxy,benzyloxy, methoxycarbonyl, amino wherein the nitrogen atom may beindependently mono or di-substituted by C1-3 alkyl or phenyl; halogen,hydroxy and carboxy;

[0154] R₈ is a heteroaryl ring selected from the group consisting ofoxazolyl, thiazolyl, imidazolyl, pyridyl, benzthiazolyl andbenzoxazolyl, wherein any of the above R₈ can be optionally substitutedby one or more R_(j);

[0155] R_(j) is selected from the group consisting of methyl, phenyl,furanyl, thienyl, benzyl, methoxy, methoxycarbonyl, acetyloxy,benzoyloxy, carbamoyl wherein the nitrogen atom may be independentlymono or di-substituted by methyl or phenyl; acetylamino, benzoylamino,ureido wherein either nitrogen atom may be independently substituted bymethyl or phenyl; methoxycarbonylamino, amino wherein the nitrogen atommay be independently mono or di-substituted by methyl or phenyl;halogen, hydroxy, carboxy and cyano, R_(j) may be further optionallysubstituted by one or more R_(k);

[0156] R_(k) is selected from the group consisting of methyl, phenyl,methoxy, phenoxy, benzyloxy, methoxycarbonyl, carbamoyl wherein thenitrogen atom may be independently mono or di-substituted by methyl orphenyl; ureido wherein either nitrogen atom may be independentlysubstituted by methyl or phenyl; benzyloxycarbonylamino,benzyloxycarbonylaminoC1-5alkyl, amino wherein the nitrogen atom may beindependently mono or di-substituted by C1-3alkyl, phenyl, furanyl orthienyl; halogen, hydroxy, carboxy, cyano and nitro.

[0157] Penultimately preferred compounds of the formula (I) are thosewherein:

[0158] R₁ is cyclohexyl, phenyl, naphthyl, piperidinyl, morpholinyl,piperazinyl, pyranyl or thiopyranyl, wherein R₁ is optionallysubstituted by one or more R_(b);

[0159] R_(b) is selected from the group consisting of, pyrrolyl,imidazolyl, indolyl, benzimidazolyl, methoxy, methoxycarbonyl, aminowherein the nitrogen atom may be independently mono or di-substituted byC1-3 alkyl; halogen, hydroxy and carboxy, R_(b) may be furtheroptionally substituted by one or more R_(c);

[0160] R_(c) is selected from the group consisting of methoxy, halogenand hydroxy;

[0161] R_(d) is selected from the group consisting of methyl, C3-6cycloalkyl, phenyl, C1-4 alkoxy, C1-3 alkanoylamino, methylthio whereinthe sulfur atom may be oxidized to a sulfoxide or sulfone, halogen,hydroxy, oxo, carboxy and cyano, R_(d) may be further optionallysubstituted by one or more R_(e);

[0162] R_(e) is selected from the group consisting of methyl, phenyl,methoxy, halogen and hydroxy;

[0163] R₅ is H;

[0164] R_(f) is selected from the group consisting of C5-6 cycloalkyl,phenyl, naphthyl, thienyl, indolyl, methoxy, methylthio wherein thesulfur atom may be oxidized to a sulfoxide or sulfone,methoxycarbonylamino, halogen, hydroxy, carboxy and cyano, R_(f) may befurther optionally substituted by one or more R_(g);

[0165] R_(g) is selected from the group consisting of methyl, phenyloptionally substituted by halogen; methoxy, phenoxy, benzyloxy,methoxycarbonyl, halogen, hydroxy and carboxy;

[0166] R₈ is a heteroaryl ring selected from the group consisting ofoxazolyl, pyridyl, benzthiazolyl and benzoxazolyl, wherein any of theabove R₈ can be optionally substituted by one or more R_(j);

[0167] R_(j) is selected from the group consisting of methyl, phenyl,benzyl, methoxy, methoxycarbonyl, acetyloxy, benzoyloxy, carbamoylwherein the nitrogen atom may be independently mono or di-substituted bymethyl or phenyl; methoxycarbonylamino, halogen, hydroxy and carboxy,R_(j) may be further optionally substituted by one or more R_(k);

[0168] R_(k) is selected from the group consisting of methyl, phenyl,methoxy, methoxycarbonyl, carbamoyl wherein the nitrogen atom may beindependently mono or di-substituted by methyl or phenyl;benzyloxycarbonylamino, amino wherein the nitrogen atom may beindependently mono or di-substituted by methyl or phenyl; halogen,hydroxy and carboxy.

[0169] Ultimately preferred compounds of the formula(I) are thosewherein:

[0170] R₁ is phenyl or 4-morpholinyl, wherein R₁ is optionallysubstituted by one or more R_(b);

[0171] R_(b) is selected from the group consisting of benzimidazolyl,methoxy and dimethylamino, R_(b) may be further optionally substitutedby a halogen atom;

[0172] R₃ is C1-5 alkyl wherein R₃ is optionally substituted by one ormore R_(d);

[0173] R_(d) is selected from the group consisting of C3-6 cycloalkyland phenyl, R_(d) may be further optionally substituted by one or moreR_(e);

[0174] R_(e) is selected from the group consisting of methyl andhalogen;

[0175] R₆ is C1-5 alkyl optionally substituted by one or more R_(f);

[0176] R_(f) is selected from the group consisting of C5-6 cycloalkyl,phenyl, methylthio wherein the sulfur atom may be oxidized to asulfoxide or sulfone, and halogen, R_(f) may be further optionallysubstituted by one or more R_(g);

[0177] R_(g) is selected from the group consisting of methyl, methoxy,methoxycarbonyl, halogen and hydroxy;

[0178] R₈ is a heteroaryl ring selected from the group consisting ofoxazolyl, pyridyl, benzthiazolyl and benzoxazolyl, wherein any of theabove R₈ can be optionally substituted by one or more R_(j);

[0179] R_(j) is selected from the group consisting of phenyl,methoxycarbonyl, carbamoyl wherein the nitrogen atom may beindependently mono or disubstituted by methyl or phenyl;methoxycarbonylamino and halogen, R_(j) may be further optionallysubstituted by one or more R_(k);

[0180] R_(k) is selected from the group consisting of phenyl,methoxycarbonyl, carbamoyl, benzyloxycarbonylamino and halogen.

[0181] In another embodiment of the invention there are provided novelcompounds of the formula (Ia):

[0182] wherein:

[0183] A is —C(Y)— or —SO₂—

[0184] —Y is O, S or NR_(a) wherein R_(a) is selected from the groupconsisting of H, alkyl, aryl, alkoxy, aryloxy, alkylamino and arylamino;

[0185] R₁ is alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl or aminowherein R₁ is optionally substituted by one or more R_(b);

[0186] R_(b) is selected from the group consisting of alkyl, cycloalkyl,aryl, heterocyclyl, heteroaryl, alkoxy, aryloxy, alkoxycarbonyl,aryloxycarbonyl, alkanoyl, aroyl, alkanoyloxy, aroyloxy, carbamoylwherein the nitrogen atom may be independently mono or di-substituted byalkyl, aryl, heterocyclyl or heteroaryl, alkanoylamino, aroylamino,alkylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, arylthio wherein the sulfur atom may be oxidized to a sulfoxideor sulfone, ureido wherein either nitrogen atom may be independentlysubstituted by alkyl, aryl, heterocyclyl or heteroaryl,alkoxycarbonylamino, aryloxycarbonylamino, alkylcarbamoyloxy,arylcarbamoyloxy, alkylsulfonylamino, arylsulfonylamino,alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atommay be independently mono or di-substituted by alkyl, aryl, heterocyclylor heteroaryl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino andguanidino, R_(b) may be further optionally substituted by one or moreR_(c);

[0187] R_(c) is selected from the group consisting of alkyl, cycloalkyl,aryl, heterocycle, heteroaryl, arylalkyl, alkoxy, aryloxy, arylalkoxy,alkanoyl, aroyl, amino wherein the nitrogen atom may be independentlymono or di-substituted by alkyl, aryl, heterocyclyl or heteroaryl,halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino;

[0188] R₂ is H or alkyl;

[0189] R₃ is H, alkyl, cycloalkyl, aryl, heterocyclyl or heteroaryl,wherein R₃ is optionally substituted by one or more groups of theformula R_(d);

[0190] R_(d) is selected from the group consisting of alkyl, cycloalkyl,aryl, heterocyclyl, heteroaryl, alkoxy, aryloxy, arylalkoxy,alkoxycarbonyl, aryloxycarbonyl, alkanoyl, aroyl, alkanoyloxy, aroyloxy,carbamoyl wherein the nitrogen atom may be independently mono ordi-substituted by alkyl, aryl, heterocyclyl or heteroaryl,alkanoylamino, aroylamino, alkylthio wherein the sulfur atom may beoxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom maybe oxidized to a sulfoxide or sulfone, ureido wherein either nitrogenatom may be independently substituted by alkyl, aryl, heterocyclyl orheteroaryl, alkoxycarbonylamino, aryloxycarbonylamino,alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino,arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino whereinthe nitrogen atom may be independently mono or di-substituted by alkyl,aryl, heterocyclyl or heteroaryl, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino, R_(d) may be further optionallysubstituted by one or more R_(d);

[0191] R_(e) is selected from the group consisting of alkyl, cycloalkyl,aryl, arylalkyl, alkoxy, aryloxy, arylalkoxy, alkanoyl, aroyl, amino,halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino;

[0192] R₄ is H or alkyl;

[0193] R₅ is H, alkyl or cycloalkyl;

[0194] R₆ is H, alkyl, cycloalkyl, aryl, heterocyclyl or heteroaryl,wherein R₆ is optionally substituted by one or more groups of theformula R_(f);

[0195] R_(f) is selected from the group consisting of alkyl, cycloalkyl,aryl, heterocyclyl, heteroaryl, alkoxy, aryloxy, alkanoyl, aroyl,arylalkoxy, heteroarylalkoxy, alkoxycarbonyl, aryloxycarbonyl,alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom may beindependently mono or di-substituted by alkyl, aryl, heterocyclyl orheteroaryl, alkanoylamino, aroylamino, alkylthio wherein the sulfur atommay be oxidized to a sulfoxide or sulfone, arylthio wherein the sulfuratom may be oxidized to a sulfoxide or sulfone, arylalkylthio whereinthe sulfur atom may be oxidized to a sulfoxide or sulfone, ureidowherein either nitrogen atom may be independently substituted by alkyl,aryl, heterocyclyl or heteroaryl, alkoxycarbonylamino,aryloxycarbonylamino, alkylcarbamoyloxy, arylcarbamoyloxy,alkylsulfonylamino, arylsulfonylamino, alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom may be independentlymono or di-substituted by alkyl, aryl, heterocyclyl or heteroaryl,halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino,R_(f) may be further optionally substituted by one or more R_(g);

[0196] R_(g) is selected from the group consisting of alkyl, cycloalkyl,aryl optionally substituted by halogen, C1-5alkyl or C1-5alkoxy,heterocyclyl, heteroaryl, alkoxy, aryloxy, arylalkoxy, alkoxycarbonyl,aryloxycarbonyl, alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogenatom may be independently mono or di-substituted by alkyl, aryl,heterocyclyl or heteroaryl; alkanoylamino, aroylamino, alkylthio whereinthe sulfur atom may be oxidized to a sulfoxide or sulfone, arylthiowherein the sulfur atom may be oxidized to a sulfoxide or sulfone,ureido wherein either nitrogen atom may be independently substituted byalkyl, aryl, heterocyclyl or heteroaryl; alkoxycarbonyl amino,aryloxycarbonylamino, alkylcarbamoyloxy, arylcarbamoyloxy,alkylsulfonylamino, arylsulfonylamino, alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom may be independentlymono or di-substituted by alkyl, aryl, heterocyclyl or heteroaryl;halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino;

[0197] or R₅ together with R₆ form a 3 to 6 membered carbocyclic ring,the carbocyclic ring being optionally substituted with one or moreR_(h);

[0198] R_(h) is selected from the group consisting of alkyl, aryl,alkoxycarbonyl, aryloxycarbonyl, arylalkoxycarbonyl, carbamoyl whereinthe nitrogen atom may be optionally mono or di-substituted with a groupselected from alkyl, cycloalkyl, aryl, arylalkyl, heterocyclyl orheteroaryl; halogen, hydroxy, carboxy and cyano;

[0199] R₇ is R₈—C(Z)-;

[0200] wherein Z is O, S, or NR_(i) wherein R_(i) is selected from thegroup consisting of H, alkyl, aryl, alkoxy, aryloxy and hydroxy;

[0201] R₈ is a 5-8 membered monocyclic heteroaryl or 8-11 memberedbicyclic heteroaryl ring system, each of the monocyclic or bicyclic ringsystems having 1-4 of the same or different heteroatoms selected fromthe group consisting of N, O and S wherein any of the above R₈ can beoptionally substituted by one or more R_(j);

[0202] R_(j) is selected from the group consisting of alkyl, cycloalkyl,aryl, heterocyclyl, heteroaryl, arylalkyl, alkoxy, aryloxy, alkanoyl,aroyl, arylalkoxy, alkoxycarbonyl, aryloxycarbonyl, alkanoyloxy,aroyloxy, carbamoyl wherein the nitrogen atom may be independently monoor di-substituted by alkyl, aryl, heterocyclyl or heteroaryl,alkanoylamino, aroylamino, alkylthio wherein the sulfur atom may beoxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom maybe oxidized to a sulfoxide or sulfone, arylalkylthio wherein the sulfuratom may be oxidized to a sulfoxide or sulfone, ureido wherein eithernitrogen atom may be independently substituted by alkyl, aryl,heterocyclyl or heteroaryl; alkoxycarbonylamino, aryloxycarbonylamino,alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino,arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino whereinthe nitrogen atom may be independently mono or di-substituted by alkyl,aryl, heterocyclyl or heteroaryl; halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino, R_(j) may be further optionallysubstituted by one or more R_(k);

[0203] R_(k) is selected from the group consisting of alkyl, cycloalkyl,aryl, heterocyclyl, heteroaryl, alkoxy, aryloxy, arylalkoxy,alkoxycarbonyl, aryloxycarbonyl, alkanoyloxy, aroyloxy, carbamoylwherein the nitrogen atom may be independently mono or di-substituted byalkyl, aryl, heterocyclyl or heteroaryl, alkanoylamino, aroylamino,alkylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, arylthio wherein the sulfur atom may be oxidized to a sulfoxideor sulfone, ureido wherein either nitrogen atom may be independentlysubstituted by alkyl, aryl, heterocyclyl or heteroaryl,alkoxycarbonylamino, aryloxycarbonylamino, arylalkoxycarbonylamino,arylalkoxycarbonylaminoalkyl, alkylcarbamoyloxy, arylcarbamoyloxy,alkylsulfonylamino, arylsulfonylamino, alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom may be independentlymono or di-substituted by alkyl, aryl, heterocyclyl or heteroaryl,halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino,wherein R_(k) may be further optionally substituted by R₁;

[0204] R₁ is selected from the group consisting of alkyl, cycloalkyl,aryl, and benzyl;

[0205] X is O, S or N—OH;

[0206] and the pharmacurtically acceptable derivatives thereof;

[0207] with the following provisos:

[0208] when R₆ is alkyl the alkyl must be substituted with R_(f) whereinR_(f) is not hydroxy, sulfhydryl or halogen; and

[0209] when R₁ is C1alkyl then R_(b) cannot be carbamoyl, alkanoylamino,aroylamino, ureido, alkoxycarbonylamino, aryloxycarbonylamino,alkylsulfonylamino, arylsulfonylamino, amino, amidino or guanidinowherein each said R_(b) is linked to said R₁ via the nitrogen atomthereof.

[0210] Preferred compounds of the formula (Ia) are those wherein:

[0211] R_(a) is selected from the group consisting of H, alkyl and aryl;

[0212] R₁ is C1-8 alkyl, C3-7 cycloalkyl, aryl, heterocyclyl selectedfrom the group consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, pyranyl, thiopyranyl, piperazinyl and indolinyl;heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, or amino wherein R1 isoptionally substituted by one or more R_(b);

[0213] R_(b) is selected from the group consisting of C1-8 alkyl, C3-7cycloalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, C1-8 alkoxy, aryloxy, C1-8alkoxycarbonyl, aryloxycarbonyl, C1-8 alkanoyloxy, aroyloxy, carbamoylwherein the nitrogen atom may be independently mono or di-substituted byC1-8 alkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl, or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, C1-8 alkanoylamino,aroylamino, C1-8 alkylthio wherein the sulfur atom may be oxidized to asulfoxide or sulfone, arylthio wherein the sulfur atom may be oxidizedto a sulfoxide or sulfone, ureido wherein either nitrogen atom may beindependently substituted by alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl, or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, alkoxycarbonylamino, aryloxycarbonylamino, C1-8alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino,arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino whereinthe nitrogen atom may be independently mono or di-substituted by alkyl,aryl, heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl,oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyridinyl,pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl and phenoxazinyl, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino, R_(b) may be further optionallysubstituted by one or more R_(c);

[0214] R_(c) is selected from the group consisting of C1-8 alkyl, C3-6cycloalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, C1-8 alkoxy, aryloxy,halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino;

[0215] R₃ is H, C1-8 alkyl, C3-7 cycloalkyl or aryl wherein R₃ isoptionally substituted by one or more R_(d);

[0216] R_(d) is selected from the group consisting of C1-8 alkyl, C3-7cycloalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, C1-8 alkoxy, aryloxy,alkanoyl, aroyl, C1-8 alkoxycarbonyl, aryloxycarbonyl, C1-8 alkanoyloxy,aroyloxy, carbamoyl wherein the nitrogen atom may be independently monoor di-substituted by C1-8 alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl, or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, C1-8 alkanoylamino, aroylamino, C1-8 alkylthio whereinthe sulfur atom may be oxidized to a sulfoxide or sulfone, arylthiowherein the sulfur atom may be oxidized to a sulfoxide or sulfone,ureido wherein either nitrogen atom may be independently substituted byalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, alkoxycarbonylamino,aryloxycarbonylamino, C1-8 alkylcarbamoyloxy, arylcarbamoyloxy,alkylsulfonylamino, arylsulfonylamino, alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom may be independentlymono or di-substituted by alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidinoand guanidino, R_(d) may be further optionally substituted by one ormore R_(e);

[0217] R_(e) is selected from the group consisting of C1-8 alkyl, C3-6cycloalkyl, aryl, arylalkyl, C1-8 alkoxy, aryloxy, arylalkoxy, aroyl,amino, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino andguanidino;

[0218] R₅ is H or alkyl;

[0219] R₆ is H, C1-8 alkyl, C3-7 cycloalkyl or aryl wherein R₆ isoptionally substituted by one or more R_(f);

[0220] R_(f) is selected from the group consisting of C1-8 alkyl, C3-7cycloalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, C1-8 alkoxy, aryloxy,arylC1-8alkoxy, heteroarylC1-8alkoxy, C1-8 alkoxycarbonyl,aryloxycarbonyl, C1-8 alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom may be independently mono or di-substituted by C1-8 alkyl,aryl, heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl,oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyridinyl,pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl and phenoxazinyl, C1-8 alkanoylamino, aroylamino, C1-8alkylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, arylthio wherein the sulfur atom may be oxidized to a sulfoxideor sulfone, arylC1-8 alkylthio wherein the sulfur atom may be oxidizedto a sulfoxide or sulfone, ureido wherein either nitrogen atom may beindependently substituted by alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, alkoxycarbonylamino, aryloxycarbonylamino, C1-8alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino,arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino whereinthe nitrogen atom may be independently mono or di-substituted by alkyl,aryl, heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl,oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyridinyl,pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl and phenoxazinyl, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino, R_(f) may be further optionallysubstituted by one or more R_(g);

[0221] R_(g) is selected from the group consisting of C1-8 alkyl, C3-7cycloalkyl, aryl optionally substituted by halogen, C1-3alkyl orC1-3alkoxy; heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, C1-8 alkoxy, aryloxy,arylC1-8alkoxy, C1-8 alkoxycarbonyl, aryloxycarbonyl, C1-8 alkanoyloxy,aroyloxy, carbamoyl wherein the nitrogen atom may be independently monoor di-substituted by C1-8 alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl, or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, C1-8 alkanoylamino, aroylamino, C1-8 alkylthio whereinthe sulfur atom may be oxidized to a sulfoxide or sulfone, arylthiowherein the sulfur atom may be oxidized to a sulfoxide or sulfone,ureido wherein either nitrogen atom may be independently substituted byalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl, or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl or phenoxazinyl, alkoxycarbonylamino,aryloxycarbonylamino, C1-8 alkylcarbamoyloxy, arylcarbamoyloxy,alkylsulfonylamino, arylsulfonylamino, alkylaminosulfonyl andarylaminosulfonyl, amino wherein the nitrogen atom may be independentlymono or di-substituted by alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl, or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidinoand guanidino;

[0222] R_(h) is selected from the group consisting of C1-8 alkyl, aryl,C1-8 alkoxycarbonyl, aryloxycarbonyl, arylC1-8alkoxycarbonyl, carbamoylwherein the nitrogen atom may be optionally mono or di-substituted witha group selected from C1-8 alkyl, C3-7 cycloalkyl, aryl, arylC1-8alkyl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl,oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyridinyl,pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl and phenoxazinyl, halogen, hydroxy, carboxy and cyano;

[0223] R₈ is a heteroaryl ring selected from the group consisting offuranyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl,isoxazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl,triazinyl, indolizinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,indazolyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, tetrazolyl,purinyl, quinolizinyl, quinolinyl, isoquinolinyl, cinnolinyl,phthalazinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, pteridinyl,carbazolyl, acridinyl and phenazinyl, wherein any of the above R₈ can beoptionally substituted by one or more R_(j);

[0224] R_(j) is selected from the group consisting of alkyl, cycloalkyl,aryl, heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl;heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl,oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyridinyl,pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl and phenoxazinyl, arylalkyl, alkoxy, aryloxy, arylalkoxy,alkoxycarbonyl, aryloxycarbonyl, alkanoyloxy, aroyloxy, carbamoylwherein the nitrogen atom may be independantly mono or di-susbstitutedby alkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, alkanoylamino, aroylamino,alkylthio wherein the sulfur atom may be oxidised to a sulfoxide orsulfone, arylthio wherein the sulfur atom may be oxidised to a sulfoxideor sulfone, arylalkylthio wherein the sulfur atom may be oxidised to asulfoxide or sulfone, ureido wherein either nitrogen atom may beindependently substituted by alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl, heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, alkoxycarbonylamino, aryloxycarbonylamino, C1-8alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino,arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino whereinthe nitrogen atom may be independently mono or di-susbstituted by alkyl,aryl, heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl;heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl,oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyridinyl,pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl and phenoxazinyl, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino, R_(j) may be further optionallysubstituted by one or more R_(k);

[0225] R_(k) is selected from the group consisting of alkyl, cycloalkyl,aryl, heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl;heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl,oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyridinyl,pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl and phenoxazinyl, alkoxy, aryloxy, arylalkoxy,alkoxycarbonyl, aryloxycarbonyl, alkanoyloxy, aroyloxy, carbamoylwherein the nitrogen atom may be independantly mono or di-susbstitutedby alkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl, heteroaryl selected from furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl,triazolyl, tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl,pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, alkanoylamino, aroylamino, alkylthio wherein thesulfur atom may be oxidised to a sulfoxide or sulfone, arylthio whereinthe sulfur atom may be oxidised to a sulfoxide or sulfone, ureidowherein either nitrogen atom may be independently substituted by alkyl,aryl, heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl,heteroaryl selected from furanyl, thienyl, pyrrolyl, oxazolyl,thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, alkoxycarbonylamino, aryloxycarbonylamino,arylalkoxycarbonylamino, arylalkoxycarbonylaminoalkyl, C1-8alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino,arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino whereinthe nitrogen atom may be independently mono or di-susbstituted by alkyl,aryl, heterocyclyl selected from pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl, heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidinoand guanidino, wherein R_(k) may be further optionally substituted byR₁;

[0226]  R₁ is selected from the group consisting of C1-5 alkyl, C3-7cycloalkyl, phenyl and benzyl; and

[0227] X is O or S.

[0228] More preferred compounds of the formula (Ia) are those wherein:

[0229] Y is O or S;

[0230] R₁ is C1-5 alkyl, C3-7 cycloalkyl, phenyl, naphthyl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, pyranyl, thiopyranyl, piperazinyl andindolinyl, heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl,tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl,isoquinolinyl, quinazolinyl and quinoxalinyl or amino wherein R₁ isoptionally substituted by one or more R_(b);

[0231] R_(b) is selected from the group consisting of C1-5 alkyl, C3-7cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl, heteroaryl selected from the group consistingof furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl,triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,quinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl, C1-5 alkoxy,aryloxy, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy,aroyloxy, carbamoyl wherein the nitrogen atom may be independently monoor di-substituted by C1-8 alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, quinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl,C1-5 alkanoylamino, aroylamino, C1-5 alkylthio wherein the sulfur atommay be oxidized to a sulfoxide or sulfone, arylthio wherein the sulfuratom may be oxidized to a sulfoxide or sulfone, ureido wherein eithernitrogen atom may be independently substituted by alkyl, aryl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl,pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, C1-5 alkoxycarbonylamino,aryloxycarbonylamino, C1-5 alkylcarbamoyloxy, arylcarbamoyloxy, C1-5alkylsulfonylamino, arylsulfonylamino, C1-5 alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom may be independentlymono or di-substituted by alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, quinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl,halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino,R_(b) may be further optionally substituted by one or more R_(c);

[0232] R_(c) is selected from the group consisting of C1-5 alkyl, C3-6cycloalkyl, aryl, heterocyclyl selected from the group consisting ofpiperidinyl, morpholinyl and piperazinyl; heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, tetrazolyl and pyridinyl, C1-5 alkoxy, aryloxy, halogen,hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino;

[0233] R₂ is H or C1-3 alkyl;

[0234] R₃ is H, C1-5 alkyl, C3-7 cycloalkyl or aryl, wherein R₃ isoptionally substituted by one or more R_(d);

[0235] R_(d) is selected from the group consisting of C1-5 alkyl, C3-7cycloalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl,tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl,isoquinolinyl, quinazolinyl and quinoxalinyl, C1-5 alkoxy, aryloxy,C1-5alkanoyl, aroyl, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom may beindependently mono or di-substituted by C1-5 alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl,pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, C1-5 alkanoylamino, aroylamino, C1-5alkylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, arylthio wherein the sulfur atom may be oxidized to a sulfoxideor sulfone, ureido wherein either nitrogen atom may be independentlysubstituted by C1-5 alkyl, aryl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl or heteroaryl selected the group consisting offuranyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl,tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl,isoquinolinyl, quinazolinyl and quinoxalinyl, C1-5 alkoxycarbonylamino,aryloxycarbonylamino, C1-5 alkylcarbamoyloxy, arylcarbamoyloxy, C1-5alkylsulfonylamino, arylsulfonylamino, C1-5 alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom may be independentlymono or di-substituted by C1-5 alkyl, aryl, heterocyclyl selected fromthe group consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, quinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl,halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino,R_(d) may be further optionally substituted by one or more R_(e);

[0236] R_(e) is selected from the group consisting of C1-5 alkyl, C3-6cycloalkyl, aryl, arylalkyl, C1-5 alkoxy, aryloxy, arylC1-5alkoxy,aroyl, amino, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino andguanidino;

[0237] R₄ is H or C1-3 alkyl;

[0238] R₅ is H or C1-8 alkyl;

[0239] R₆ is H, C1-5 alkyl, C3-7 cycloalkyl or aryl wherein R₆ isoptionally substituted by one or more R_(f);

[0240] R_(f) is selected from the group consisting of C1-5 alkyl, C3-7cycloalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl,tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl,isoquinolinyl, quinazolinyl and quinoxalinyl, C1-5 alkoxy, aryloxy,arylC1-5alkoxy, heteroarylC1-5alkoxy, C1-5 alkoxycarbonyl,aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom may be independently mono or di-substituted by C1-5 alkyl,aryl, heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl,pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, C1-5 alkanoylamino, aroylamino, C1-5alkylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, arylthio wherein the sulfur atom may be oxidized to a sulfoxideor sulfone, arylC1-5 alkylthio wherein the sulfur atom may be oxidizedto a sulfoxide or sulfone, ureido wherein either nitrogen atom may beindependently substituted by C1-5 alkyl, aryl, heterocyclyl selectedfrom the group consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, quinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl,C1-5 alkoxycarbonylamino, aryloxycarbonylamino, C1-5 alkylcarbamoyloxy,arylcarbamoyloxy, C1-5 alkylsulfonylamino, arylsulfonylamino, C1-5alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atommay be independently mono or di-substituted by C1-5 alkyl, aryl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl,pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino, R_(f) may be further optionallysubstituted by one or more R_(g);

[0241] R_(g) is selected from the group consisting of C1-5 alkyl, C3-7cycloalkyl, aryl optionally substituted by halogen, methyl or methoxy;heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl;heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl,pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, C1-5 alkoxy, aryloxy, arylC1-5alkoxy,C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy,carbamoyl wherein the nitrogen atom may be independently mono ordi-substituted by C1-5 alkyl, aryl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, quinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl,C1-5 alkanoylamino, aroylamino, C1-5 alkylthio wherein the sulfur atommay be oxidized to a sulfoxide or sulfone, arylthio wherein the sulfuratom may be oxidized to a sulfoxide or sulfone, ureido wherein eithernitrogen atom may be independently substituted by C1-5 alkyl, aryl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl,pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, C1-5 alkoxycarbonylamino,aryloxycarbonylamino, C1-5 alkylcarbamoyloxy, arylcarbamoyloxy, C1-5alkylsulfonylamino, arylsulfonylamino, C1-5 alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom may be independentlymono or di-substituted by C1-5 alkyl, aryl, heterocyclyl selected fromthe group consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, quinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl,halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino;

[0242] R_(h) is selected from the group consisting of C1-5 alkyl, aryl,C1-5 alkoxycarbonyl, aryloxycarbonyl, arylC1-5alkoxycarbonyl, carbamoylwherein the nitrogen atom may be optionally mono or di-substituted witha group selected from C1-5 alkyl, C3-7 cycloalkyl, aryl, arylC1-5alkyl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl,pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, halogen, hydroxy, carboxy and cyano;

[0243] R_(i) is alkoxy, aryloxy or hydroxy;

[0244] R₈ is a heteroaryl ring selected from the group consisting offuranyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl,isoxazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl,triazinyl, indolizinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,indazolyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl,quinolizinyl, quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl,quinazolinyl, quinoxalinyl, naphthyridinyl, pteridinyl, carbazolyl,acridinyl and phenazinyl, wherein any of the above R₈ can be optionallysubstituted by one or more R_(j);

[0245] R_(j) is selected from the group consisting of C1-8alkyl,C3-7cycloalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl; arylC1-8alkyl, C1-8alkoxy,aryloxy, arylC1-8alkoxy, C1-8alkoxycarbonyl, aryloxycarbonyl,C1-8alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom may beindependantly mono or di-susbstituted by C1-8alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl; heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl,triazolyl, tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl,pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, C1-8alkanoylamino, aroylamino, C1-8alkylthio whereinthe sulfur atom may be oxidised to a sulfoxide or sulfone, arylthiowherein the sulfur atom may be oxidised to a sulfoxide or sulfone,arylC1-8alkylthio wherein the sulfur atom may be oxidised to a sulfoxideor sulfone, ureido wherein either nitrogen atom may be independentlysubstituted by C1-8 alkyl, aryl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl; heteroaryl selected from the group consistingof furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl,isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl,thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl,isoindolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, purinyl, quinolinyl, isoquinolinyl, quinazolinyl,quinoxalinyl, carbazolyl, phenothiazinyl and phenoxazinyl,alkoxycarbonylamino, aryloxycarbonylamino, C1-8 alkylcarbamoyloxy,arylcarbamoyloxy, alkylsulfonylamino, arylsulfonylamino,alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atommay be independently mono or di-susbstituted by C1-8 alkyl, aryl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl;heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl,oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyridinyl,pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl and phenoxazinyl, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino, R_(j) may be further optionallysubstituted by one or more R_(k);

[0246] R_(k) is selected from the group consisting of C1-8 alkyl, C3-7cycloalkyl, aryl, heterocyclyl selected from pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl,triazolyl, tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl,pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, C1-8 alkoxy, aryloxy, arylC1-8alkoxy,C1-8alkoxycarbonyl, aryloxycarbonyl, C1-8alkanoyloxy, aroyloxy,carbamoyl wherein the nitrogen atom may be independantly mono ordi-susbstituted by C1-8alkyl, aryl, heterocyclyl selected frompyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, alkanoylamino, aroylamino,C1-8alkylthio wherein the sulfur atom may be oxidised to a sulfoxide orsulfone, arylthio wherein the sulfur atom may be oxidised to a sulfoxideor sulfone, ureido wherein either nitrogen atom may be independentlysubstituted by C1-8alkyl, aryl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl, heteroaryl selected from the group consistingof furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl,isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl,thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl,isoindolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, purinyl, quinolinyl, isoquinolinyl, quinazolinyl,quinoxalinyl, carbazolyl, phenothiazinyl and phenoxazinyl,C1-8alkoxycarbonylamino, aryloxycarbonylamino,arylC1-8alkoxycarbonylamino, arylalkoxycarbonylaminoC1-8alkyl, C1-8alkylcarbamoyloxy, arylcarbamoyloxy, C1-8alkylsulfonylamino,arylsulfonylamino, C1-8alkylaminosulfonyl, arylaminosulfonyl, aminowherein the nitrogen atom may be independently mono or di-susbstitutedby C1-8alkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, halogen, hydroxy, oxo,carboxy, cyano, nitro, amidino and guanidino, wherein R_(k) may befurther optionally substituted by R₁.

[0247] Even more preferred compounds of the formula (Ia) are thosewherein:

[0248] Y is O;

[0249] R₁ is C1-5 alkyl, C3-7 cycloalkyl, phenyl, naphthyl, heterocyclylselected from the group consisting of piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl, pyranyl and thiopyranyl, heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyland isoquinolinyl, or amino wherein R₁ is optionally substituted by oneor more R_(b);

[0250] R_(b) is selected from the group consisting of C1-5 alkyl, C3-7cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl; heteroaryl selected from the group consistingof furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl,tetrazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl andisoquinolinyl; C1-5 alkoxy, aryloxy, C1-5 alkoxycarbonyl,aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom may be independently mono or di-substituted by C1-5 alkyl,phenyl, naphthyl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, piperazinyl and indolinyl, orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, tetrazolyl, pyridinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, quinolinyl and isoquinolinyl, C1-5 alkanoylamino,aroylamino, C1-5 alkylthio wherein the sulfur atom may be oxidized to asulfoxide or sulfone, arylthio wherein the sulfur atom may be oxidizedto a sulfoxide or sulfone, ureido wherein either nitrogen atom may beindependently substituted by alkyl or aryl; C1-5 alkoxycarbonylamino,aryloxycarbonylamino, C1-5 alkylcarbamoyloxy, arylcarbamoyloxy, C1-5alkylsulfonylamino, arylsulfonylamino, C1-5 alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom may be independentlymono or di-substituted by alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl andisoquinolinyl, halogen, hydroxy, oxo, carboxy, cyano and nitro, R_(b)may be further optionally substituted by one or more R_(c);

[0251] R_(c) is selected from the group consisting of C1-5 alkyl, C3-6cycloalkyl, aryl, C1-5 alkoxy, aryloxy, halogen, hydroxy, oxo, carboxy,and cyano;

[0252] R₂ is H or methyl;

[0253] R₃ is H, C1-5 alkyl, C3-7 cycloalkyl or phenyl, wherein R₃ isoptionally substituted by one or more R_(d);

[0254] R_(d) is selected from the group consisting of C1-3 alkyl, C3-6cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of piperidinyl, morpholinyl and piperazinyl; heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyland isoquinolinyl, C1-5 alkoxy, aryloxy, aroyl, C1-5 alkoxycarbonyl,aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom may be independently mono or di-substituted by C1-5 alkyl,aryl, heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl and piperazinyl or heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl andisoquinolinyl, C1-5 alkanoylamino, aroylamino, C1-5 alkylthio whereinthe sulfur atom may be oxidized to a sulfoxide or sulfone, arylthiowherein the sulfur atom may be oxidized to a sulfoxide or sulfone,ureido wherein either nitrogen atom may be independently substituted byC1-5 alkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of piperidinyl, morpholinyl and piperazinyl or heteroarylselected the group consisting of furanyl, thienyl, pyrrolyl, oxazolyl,thiazolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl andisoquinolinyl, C1-5 alkoxycarbonylamino, aryloxycarbonylamino, C1-5alkylcarbamoyloxy, arylcarbamoyloxy, C1-5 alkylsulfonylamino,arylsulfonylamino, C1-5 alkylaminosulfonyl, arylaminosulfonyl, aminowherein the nitrogen atom may be independently mono or di-substituted byC1-5 alkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of piperidinyl, morpholinyl and piperazinyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyland isoquinolinyl, halogen, hydroxy, oxo, carboxy and cyano, R_(e) maybe further optionally substituted by one or more R_(e);

[0255] R_(e) is selected from the group consisting of C1-5 alkyl, C3-6cycloalkyl, aryl, arylC1-5alkyl, C1-5 alkoxy, aryloxy, arylC1-3alkoxy,aroyl, amino, halogen, hydroxy, oxo, carboxy and cyano;

[0256] R₄ is H or methyl;

[0257] R₅ is H or C1-5 alkyl;

[0258] R₆ is H, C1-5 alkyl, C3-7 cycloalkyl, phenyl or naphthyl whereinR₆ is optionally substituted by one or more R_(f);

[0259] R_(f) is selected from the group consisting of C1-5 alkyl, C3-7cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl; heteroaryl selected from the group consistingof furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl,triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,quinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl, C1-5 alkoxy,aryloxy, arylC1-5 alkoxy, pyridylC1-5alkoxy, thienylC1-5alkoxy,furanylC1-5alkoxy, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom may beindependently mono or di-substituted by C1-5 alkyl, aryl, heterocyclylselected from the group consisting of piperidinyl, morpholinyl andpiperazinyl or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,quinolinyl and isoquinolinyl, C1-5 alkanoylamino, aroylamino, C1-5alkylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, arylthio wherein the sulfur atom may be oxidized to a sulfoxideor sulfone, arylC1-5 alkylthio wherein the sulfur atom may be oxidizedto a sulfoxide or sulfone, ureido wherein either nitrogen atom may beindependently substituted by C1-5 alkyl, aryl, heterocyclyl selectedfrom the group consisting of piperidinyl, morpholinyl and piperazinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,quinolinyl and isoquinolinyl, C1-5 alkoxycarbonylamino,aryloxycarbonylamino, C1-5 alkylcarbamoyloxy, arylcarbamoyloxy, C1-5alkylsulfonylamino, arylsulfonylamino, C1-5 alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom may be independentlymono or di-substituted by C1-5 alkyl, aryl, heterocyclyl selected fromthe group consisting of pyrrolidinyl, piperidinyl, morpholinyl andpiperazinyl or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,quinolinyl and isoquinolinyl, halogen, hydroxy, oxo, carboxy and cyano,R_(f) may be further optionally substituted by one or more R_(g);

[0260] R_(g) is selected from the group consisting of C1-5 alkyl, C3-7cycloalkyl, phenyl optionally substituted by halogen, methyl or methoxy;naphthyl optionally substituted by halogen, methyl or methoxy;heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl;heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl,pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, C1-5 alkoxy, aryloxy, arylC1-5alkoxy,C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy,carbamoyl wherein the nitrogen atom may be independently mono ordi-substituted by C1-5 alkyl, aryl, heterocyclyl selected from the groupconsisting of piperidinyl, morpholinyl and piperazinyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyland isoquinolinyl, C1-5 alkanoylamino, aroylamino, C1-5 alkylthiowherein the sulfur atom may be oxidized to a sulfoxide or sulfone,arylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, ureido wherein either nitrogen atom may be independentlysubstituted by C1-5 alkyl, aryl, heterocyclyl selected from the groupconsisting of piperidinyl, morpholinyl and piperazinyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl,isoquinolinyl, C1-5 alkoxycarbonylamino, aryloxycarbonylamino, C1-5alkylcarbamoyloxy, arylcarbamoyloxy, C1-5 alkylsulfonylamino,arylsulfonylamino, C1-5 alkylaminosulfonyl, arylaminosulfonyl, aminowherein the nitrogen atom may be independently mono or di-substituted byC1-5 alkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl and piperazinyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyland isoquinolinyl, halogen, hydroxy, oxo, carboxy and cyano;

[0261] R_(h) is selected from the group consisting of C1-5 alkyl,phenyl, naphthyl, C1-5 alkoxycarbonyl, aryloxycarbonyl,arylC1-3alkoxycarbonyl, carbamoyl wherein the nitrogen atom may beoptionally mono or di-substituted with a group selected from C1-5 alkyl,C3-6 cycloalkyl, phenyl, naphthyl, arylC1-3alkyl, heterocyclyl selectedfrom the group consisting of pyrrolidinyl, piperidinyl, morpholinyl andpiperazinyl or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,quinolinyl and isoquinolinyl, halogen, hydroxy, carboxy and cyano;

[0262] Z is O or S;

[0263] R₈ is a heteroaryl ring selected from the group consisting offuranyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl,isoxazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl,triazinyl, indolizinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,indazolyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl,quinolizinyl, quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl,quinazolinyl, quinoxalinyl, naphthyridinyl, pteridinyl, carbazolyl,acridinyl and phenazinyl, wherein any of the above R₈ can be optionallysubstituted by one or more groups of the formula R_(j);

[0264] R_(j) is selected from the group consisting of C1-5alkyl,C3-6cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl and piperazinyl;heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, tetrazolyl, pyridinyl,pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyland isoquinolinyl, arylC1-5alkyl, C1-5alkoxy, aryloxy, arylC1-5alkoxy,C1-5alkoxycarbonyl, aryloxycarbonyl, C1-5alkanoyloxy, aroyloxy,carbamoyl wherein the nitrogen atom may be independantly mono ordi-susbstituted by C1-5alkyl, aryl, heterocyclyl selected from the groupconsisting of piperidinyl, morpholinyl and piperazinyl, heteroarylselected from furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, tetrazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl andisoquinolinyl, C1-5alkanoylamino, aroylamino, C1-5alkylthio wherein thesulfur atom may be oxidised to a sulfoxide or sulfone, arylthio whereinthe sulfur atom may be oxidised to a sulfoxide or sulfone,arylC1-5alkylthio wherein the sulfur atom may be oxidised to a sulfoxideor sulfone, ureido wherein either nitrogen atom may be independentlysubstituted by C1-5 alkyl, aryl, heterocyclyl selected from the groupconsisting of piperidinyl, morpholinyl and piperazinyl; heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, tetrazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,quinolinyl and isoquinolinyl, C1-5alkoxycarbonylamino,aryloxycarbonylamino, C1-5 alkylcarbamoyloxy, arylcarbamoyloxy,C1-5alkylsulfonylamino, arylsulfonylamino, C1-5alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom may be independentlymono or di-susbstituted by C1-5 alkyl, aryl, heterocyclyl selected fromthe group consisting of piperidinyl, morpholinyl and piperazinyl;heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, tetrazolyl, pyridinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, purinyl, quinolinyl and isoquinolinyl, halogen, hydroxy,oxo, carboxy, cyano, nitro, amidino and guanidino, wherein R_(j) may befurther optionally substituted by one or more R_(k);

[0265] R_(k) is selected from the group consisting of C1-3 alkyl, C3-6cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl and piperazinyl;heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, tetrazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl,C1-3 alkoxy, aryloxy, arylC1-3 alkoxy, C1-3 alkoxycarbonyl,aryloxycarbonyl, C1-3 alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom may be independantly mono or di-susbstituted by C1-3alkyl, aryl, heterocyclyl selected from the group consisting ofmorpholinyl and piperazinyl; heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, tetrazolyl, and pyridinyl, C1-3alkanoylamino, aroylamino,C1-3alkylthio wherein the sulfur atom may be oxidised to a sulfoxide orsulfone, arylthio wherein the sulfur atom may be oxidised to a sulfoxideor sulfone, ureido wherein either nitrogen atom may be independentlysubstituted by C1-3alkyl, phenyl, naphthyl, heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, tetrazolyl and pyridinyl, C1-3alkoxycarbonylamino,aryloxycarbonylamino, arylC1-3 alkoxycarbonylamino,benzyloxycarbonylaminoC1-5 alkyl, C1-3 alkylcarbamoyloxy,arylcarbamoyloxy, C1-3alkylsulfonylamino, arylsulfonylamino,C1-3alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogenatom may be independently mono or di-susbstituted by C1-3alkyl, aryl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl and piperazinyl; heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, tetrazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, quinolinyl and isoquinolinyl, halogen, hydroxy, oxo,carboxy, cyano and nitro, wherein R_(k) may be further optionallysubstituted by R₁;

[0266] R₁ is selected from the group consisting of C1-5 alkyl, C3-7cycloalkyl and phenyl.

[0267] Yet even more preferred compounds of the formula (Ia) are thosewherein:

[0268] R₁ is C1-5 alkyl, C3-6 cycloalkyl, phenyl, naphthyl, heterocyclylselected from the group consisting of piperidinyl, morpholinyl,piperazinyl, pyranyl and thiopyranyl; heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl andisoquinolinyl, or amino, wherein R₁ is optionally substituted by one ormore R_(b);

[0269] R_(b) is selected from the group consisting of C1-3 alkyl, C3-6cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl and piperazinyl,heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, tetrazolyl, pyridinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, quinolinyl and isoquinolinyl, C1-3 alkoxy, phenoxy, C1-3alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoylwherein the nitrogen atom may be independently mono or di-substituted byC1-5 alkyl, phenyl or heteroaryl selected from the group consisting offuranyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, quinolinyl and isoquinolinyl, C1-5 alkanoylamino,aroylamino, C1-5 alkylthio wherein the sulfur atom may be oxidized to asulfoxide or sulfone, arylthio wherein the sulfur atom may be oxidizedto a sulfoxide or sulfone, ureido wherein either nitrogen atom may beindependently substituted by C1-5alkyl, phenyl or naphthyl; C1-5alkoxycarbonylamino, C1-5 alkylcarbamoyloxy, arylcarbamoyloxy, C1-5alkylsulfonylamino, arylsulfonylamino, C1-5 alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom may be independentlymono or di-substituted by C1-5alkyl, phenyl, naphthyl, heterocyclylselected from the group consisting of piperidinyl, morpholinyl andpiperazinyl or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,quinolinyl and isoquinolinyl, halogen, hydroxy, oxo, carboxy and cyano,R_(b) may be further optionally substituted by one or more R_(c);

[0270] R_(c) is selected from the group consisting of C1-3 alkyl, C5-6cycloalkyl, aryl, C1-3 alkoxy, phenoxy, halogen, hydroxy, oxo, carboxyand cyano;

[0271] R₂ is H;

[0272] R₃ is C1-5 alkyl, C3-6 cycloalkyl or phenyl, wherein R₃ isoptionally substituted by one or more R_(d);

[0273] R_(d) is selected from the group consisting of C1-3 alkyl, C3-6cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of piperidinyl, morpholinyl and piperazinyl; heteroarylselected from the group consisting of furanyl, thienyl, thiazolyl,imidazolyl, pyridinyl, indolyl, quinolinyl and isoquinolinyl, C1-5alkoxy, phenoxy, aroyl, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom may beindependently mono or di-substituted by C1-5 alkyl, phenyl, naphthyl,heterocyclyl selected from the group consisting of piperidinyl,morpholinyl and piperazinyl or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl and indolyl, C1-5 alkanoylamino, aroylamino, C1-3alkylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, phenylthio wherein the sulfur atom may be oxidized to asulfoxide or sulfone, ureido wherein either nitrogen atom may beindependently substituted by C1-3 alkyl, phenyl or heteroaryl selectedthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl and indolyl, C1-5 alkoxycarbonylamino, C1-5alkylcarbamoyloxy, arylcarbamoyloxy, C1-5 alkylsulfonylamino,arylsulfonylamino, amino wherein the nitrogen atom may be independentlymono or di-substituted by C1-3 alkyl, phenyl, heterocyclyl selected fromthe group consisting of piperidinyl, morpholinyl and piperazinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl and indolyl,halogen, hydroxy, oxo, carboxy and cyano, R_(d) may be furtheroptionally substituted by one or more R_(e);

[0274] R_(e) is selected from the group consisting of C1-5 alkyl, C5-6cycloalkyl, phenyl, naphthyl, arylC1-3alkyl, C1-5 alkoxy, phenoxy,arylC1-3alkoxy, aroyl, amino, halogen, hydroxy, oxo, carboxy and cyano;

[0275] wherein the configuration at the stereocenter defined by R₂ andR₃ and the carbon they are attached to is L;

[0276] R₄ is H;

[0277] R₅ is H or C1-3 alkyl;

[0278] R₆ is H, C1-5 alkyl, C3-6 cycloalkyl or phenyl. wherein R₆ isoptionally substituted by one or more R_(f);

[0279] R_(f) is selected from the group consisting of C1-3 alkyl, C3-6cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl and piperazinyl;heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,quinolinyl and isoquinolinyl, C1-5 alkoxy, aryloxy, arylC1-3alkoxy,pyridylC1-5alkoxy, thienylC1-5alkoxy, furanylC1-5alkoxy, C1-5alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoylwherein the nitrogen atom may be independently mono or di-substituted byC1-5 alkyl, phenyl or heteroaryl selected from the group consisting offuranyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyland indolyl, C1-5 alkanoylamino, aroylamino, C1-3 alkylthio wherein thesulfur atom may be oxidized to a sulfoxide or sulfone, arylthio whereinthe sulfur atom may be oxidized to a sulfoxide or sulfone,arylC1-3alkylthio wherein the sulfur atom may be oxidized to a sulfoxideor sulfone, ureido wherein either nitrogen atom may be independentlysubstituted by C1-5 alkyl or phenyl; C1-5 alkoxycarbonylamino, C1-5alkylsulfonylamino, arylsulfonylamino, amino wherein the nitrogen atommay be independently mono or di-substituted by C1-5 alkyl, phenyl,naphthyl, heterocyclyl selected from the group consisting ofpiperidinyl, morpholinyl and piperazinyl or heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl and indolyl, halogen, hydroxy, oxo, carboxy andcyano, R_(f) may be further optionally substituted by one or more R_(g);

[0280] R_(g) is selected from the group consisting of C1-3 alkyl, C5-6cycloalkyl, phenyl optionally substituted by halogen, methyl or methoxy;heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl and piperazinyl; heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, pyrimidinyl, pyrazinyl and indolyl, C1-5 alkoxy,aryloxy, arylC1-3alkoxy, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom may beindependently mono or di-substituted by C1-5 alkyl or aryl; C1-5alkanoylamino, aroylamino, C1-5 alkylthio wherein the sulfur atom may beoxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom maybe oxidized to a sulfoxide or sulfone, ureido wherein either nitrogenatom may be independently substituted by C1-5 alkyl or aryl; C1-5alkoxycarbonylamino, aryloxycarbonylamino, C1-5 alkylcarbamoyloxy,arylcarbamoyloxy, C1-5 alkylsulfonylamino, arylsulfonylamino, C1-5alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atommay be independently mono or di-substituted by C1-5 alkyl or aryl;halogen, hydroxy, oxo, carboxy and cyano;

[0281] R_(h) is selected from the group consisting of C1-5 alkyl,phenyl, C1-5 alkoxycarbonyl, aryloxycarbonyl, arylC1-3alkoxycarbonyl,carbamoyl wherein the nitrogen atom may be optionally mono ordi-substituted with C1-5 alkyl, C3-6 cycloalkyl, phenyl, naphthyl,arylC1-3alkyl, halogen, hydroxy, carboxy and cyano;

[0282] wherein Z is O;

[0283] R₈ is a heteroaryl ring selected from the group consisting ofoxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl,pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl,isoquinolinyl, quinazolinyl and quinoxalinyl, wherein any of the aboveR₈ can be optionally substituted by one or more R_(j);

[0284] R_(j) is selected from the group consisting of C1-5 alkyl, C5-6cycloalkyl, phenyl, naphthyl, pyrrolidinyl, piperidinyl, morpholinyl,piperazinyl, furanyl, thienyl, pyrrolyl, tetrazolyl, pyridinyl,pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,arylC1-3alkyl, C1-3alkoxy, aryloxy, arylC1-3alkoxy, C1-3alkoxycarbonyl,aryloxycarbonyl, C1-3alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom may be independantly mono or di-susbstituted by C1-3alkyl,phenyl, naphthyl, piperidinyl, furanyl, thienyl, pyrrolyl, oxazolyl,thiazolyl, imidazolyl, tetrazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyland isoquinolinyl; C1-3alkanoylamino, aroylamino, C1-3alkylthio whereinthe sulfur atom may be oxidised to a sulfoxide or sulfone, arylthiowherein the sulfur atom may be oxidised to a sulfoxide or sulfone,arylC1-3alkylthio wherein the sulfur atom may be oxidised to a sulfoxideor sulfone, ureido wherein either nitrogen atom may be independentlysubstituted by C1-3 alkyl, phenyl, naphthyl, piperidinyl, morpholinyl,thiazolyl, imidazolyl, tetrazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyland isoquinolinyl; C1-3 alkoxycarbonylamino, aryloxycarbonylamino, C1-3alkylcarbamoyloxy, arylcarbamoyloxy, C1-3 alkylsulfonylamino,arylsulfonylamino, C1-3alkylaminosulfonyl, arylaminosulfonyl, aminowherein the nitrogen atom may be independently mono or di-susbstitutedby C1-3 alkyl, phenyl, naphthyl, piperidinyl, furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, tetrazolyl, pyridinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, quinolinyl and isoquinolinyl; halogen, hydroxy, oxo,carboxy, cyano and nitro, R_(j) may be further optionally substituted byone or more R_(k);

[0285] R_(k) is selected from the group consisting of methyl, C5-6cycloalkyl, phenyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl,furanyl, thienyl, pyrrolyl, tetrazolyl, pyridinyl, pyrimidinyl, C1-3alkoxy, phenoxy, benzyloxy, methoxycarbonyl, acetyloxy, benzoyloxy,carbamoyl wherein the nitrogen atom may be independantly mono ordi-susbstituted by C1-3 alkyl, phenyl, furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl or pyridinyl; acetylamino, benzoylamino,methylthio wherein the sulfur atom may be oxidised to a sulfoxide orsulfone, ureido wherein either nitrogen atom may be independentlysubstituted by methyl, phenyl, furanyl, thienyl, pyrrolyl, oxazolyl,thiazolyl, imidazolyl or pyridinyl; arylC1-3alkoxycarbonylamino,benzyloxycarbonylaminoC1-5alkyl, methylcarbamoyloxy, amino wherein thenitrogen atom may be independently mono or di-susbstituted by C1-3alkyl,phenyl, naphthyl, pyrrolidinyl, piperidinyl, furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyridinyl, pyrimidinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,quinolinyl or isoquinolinyl, halogen, hydroxy, oxo, carboxy, cyano andnitro, wherein R_(k) may be further optionally substituted by R₁;

[0286] R₁ is selected from the group consisting of C1-3 alkyl, C3-6cycloalkyl and phenyl.

[0287] Still yet even more preferred compounds of the formula (Ia) arethose wherein:

[0288] R₁ is C1-3 alkyl, C5-6 cycloalkyl, phenyl, naphthyl, heterocyclylselected from the group consisting of piperidinyl, morpholinyl,piperazinyl, pyranyl and thiopyranyl; heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl and indolyl, or amino, wherein R₁ is optionallysubstituted by one or more R_(b);

[0289] R_(b) is selected from the group consisting of C1-3 alkyl, C5-6cycloalkyl, phenyl, heterocyclyl selected from the group consisting ofpiperidinyl, morpholinyl and piperazinyl; heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, imidazolyl, tetrazolyl,pyridinyl, indolyl, benzofuranyl, benzothienyl, benzimidazolyl,benzthiazolyl, benzoxazolyl, quinolinyl and isoquinolinyl, C1-3 alkoxy,C1-3 alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy,carbamoyl wherein the nitrogen atom may be independently mono ordi-substituted by C1-3 alkyl, phenyl or heteroaryl selected from thegroup consisting of pyrrolyl, imidazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl and benzthiazolyl; C1-5alkanoylamino, aroylamino, C1-3 alkylthio wherein the sulfur atom may beoxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom maybe oxidized to a sulfoxide or sulfone, ureido wherein either nitrogenatom may be independently substituted by C1-3alkyl or phenyl; C1-5alkylsulfonylamino, arylsulfonylamino, amino wherein the nitrogen atommay be independently mono or di-substituted by C1-3alkyl, phenyl,heterocyclyl selected from the group consisting of piperidinyl,morpholinyl and piperazinyl or heteroaryl selected from the groupconsisting of pyrrolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyland isoquinolinyl; halogen, hydroxy, oxo, carboxy and cyano, R_(b) maybe further optionally substituted by one or more R_(c);

[0290] R_(c) is selected from the group consisting of C1-3 alkyl, C5-6cycloalkyl, C1-3 alkoxy, halogen and hydroxy;

[0291] R₃ is C1-5 alkyl, C5-6 cycloalkyl or phenyl wherein R₃ isoptionally substituted by one or more R_(d);

[0292] R_(d) is selected from the group consisting of C1-3 alkyl, C3-6cycloalkyl, phenyl, naphthyl, 4-piperidinyl, 4-morpholinyl, piperazinyl,furanyl, thienyl, thiazolyl, imidazolyl, pyridinyl, indolyl, C1-5alkoxy, phenoxy, aroyl, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom may beindependently mono or di-substituted by C1-5 alkyl or phenyl; C1-5alkanoylamino, C1-3 alkylthio wherein the sulfur atom may be oxidized toa sulfoxide or sulfone, ureido wherein either nitrogen atom may beindependently substituted by C1-3 alkyl or phenyl; C1-5alkoxycarbonylamino, C1-5 alkylsulfonylamino, arylsulfonylamino, aminowherein the nitrogen atom may be independently mono or di-substituted byC1-3 alkyl or phenyl; halogen, hydroxy, oxo, carboxy and cyano, R_(d)may be further optionally substituted by one or more R_(e);

[0293] R_(e) is selected from the group consisting of C1-5 alkyl, C5-6cycloalkyl, phenyl, benzyl, C1-5 alkoxy, phenoxy, benzyloxy, aroyl,halogen, hydroxy, oxo, carboxy and cyano;

[0294] R₆ is H, C1-5 alkyl or phenyl wherein R₆ is optionallysubstituted by one or more R_(f);

[0295] R_(f) is selected from the group consisting of C1-3 alkyl, C3-6cycloalkyl, phenyl, naphthyl, furanyl, thienyl, thiazolyl, imidazolyl,pyridinyl, indolyl, C1-3 alkoxy, benzyloxy, pyridyl, C1-3alkoxy,thienylC1-3alkoxy, furanylC1-3alkoxy, C1-3 alkoxycarbonyl,phenoxyoxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom may be independently mono or di-substituted by C1-3 alkylor phenyl; C1-5 alkanoylamino, aroylamino, methylthio wherein the sulfuratom may be oxidized to a sulfoxide or sulfone, benzylthio wherein thesulfur atom may be oxidized to a sulfoxide or sulfone, ureido whereineither nitrogen atom may be independently substituted by C1-5 alkyl orphenyl; C1-3 alkoxycarbonylamino, amino wherein the nitrogen atom may beindependently mono or di-substituted by C1-5 alkyl or phenyl; halogen,hydroxy, oxo, carboxy and cyano, R_(f) may be further optionallysubstituted by one or more R_(g);

[0296] R_(g) is selected from the group consisting of C1-3 alkyl, phenyloptionally substituted by halogen, methyl or methoxy; heterocyclylselected from the group consisting of piperidinyl, morpholinyl andpiperazinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl and pyridinyl, C1-3 alkoxy, aryloxy, benzyloxy, C1-5alkoxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom may be independently mono or di-substituted by C1-5 alkylor phenyl; C1-5 alkanoylamino, aroylamino, C1-5 alkylthio wherein thesulfur atom may be oxidized to a sulfoxide or sulfone, ureido whereineither nitrogen atom may be independently substituted by C1-5 alkyl orphenyl; C1-5 alkoxycarbonylamino, C1-5 alkylcarbamoyloxy,arylcarbamoyloxy, C1-3 alkylsulfonylamino, arylsulfonylamino, C1-3alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atommay be independently mono or di-substituted by C1-3 alkyl or phenyl;halogen, hydroxy, oxo, carboxy and cyano;

[0297] R_(h) is selected from the group consisting of C1-3 alkyl,phenyl, C1-3 alkoxycarbonyl, phenoxyoxycarbonyl, benzyloxy, carbamoylwherein the nitrogen atom may be optionally mono or di-substituted withC1-5 alkyl, phenyl, benzyl, halogen, hydroxy, carboxy and cyano;

[0298] R₈ is a heteroaryl ring selected from the group consisting ofoxazolyl, thiazolyl, imidazolyl, pyrazolyl, pyridyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,quinolinyl and isoquinolinyl, wherein any of the above R8 can beoptionally substituted by one or more R_(j);

[0299] R_(j) is selected from the group consisting of C1-5 alkyl, C5-6cycloalkyl, phenyl, naphthyl, pyrrolidinyl, piperidinyl, morpholinyl,piperazinyl, furanyl, thienyl, pyrrolyl, tetrazolyl, pyridinyl,pyrimidinyl, benzyl, C1-3alkoxy, phenoxy, benzyloxy, C1-3alkoxycarbonyl,acetyloxy, benzoyloxy, carbamoyl wherein the nitrogen atom may beindependantly mono or di-susbstituted by methyl, phenyl, furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl and pyridinyl;acetylamino, benzoylamino, methylthio wherein the sulfur atom may beoxidised to a sulfoxide or sulfone, benzylthio wherein the sulfur atommay be oxidised to a sulfoxide or sulfone, ureido wherein eithernitrogen atom may be independently substituted by methyl, phenyl,thiazolyl, imidazolyl and pyridinyl; C1-3 alkoxycarbonylamino, C1-3alkylcarbamoyloxy, arylcarbamoyloxy, C1-3alkylsulfonylamino,arylsulfonylamino, amino wherein the nitrogen atom may be independentlymono or di-susbstituted by methyl, phenyl, furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl and pyridinyl; halogen, hydroxy,carboxy, cyano and nitro, R_(j) may be further optionally substituted byone or more R_(k);

[0300] R_(k) is selected from the group consisting of methyl, C5-6cycloalkyl, phenyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl,furanyl, thienyl, pyrrolyl, pyridinyl, C1-3 alkoxy, phenoxy, benzyloxy,methoxycarbonyl, acetyloxy, benzoyloxy, carbamoyl wherein the nitrogenatom may be independantly mono or di-susbstituted by methyl, phenyl,furanyl, thienyl; acetylamino, benzoylamino, methylthio wherein thesulfur atom may be oxidised to a sulfoxide or sulfone, ureido whereineither nitrogen atom may be independently substituted by methyl, phenyl,furanyl, thienyl, pyrrolyl, oxazolyl and thiazolyl,benzyloxycarbonylamino, benzyloxycarbonylaminoC1-5alkyl, amino whereinthe nitrogen atom may be independently mono or di-susbstituted byC1-3alkyl, phenyl, furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl and pyridinyl, halogen, hydroxy, carboxy, cyano and nitro,wherein R_(k) may be further optionally substituted by R₁;

[0301] R₁ is selected from the group consisting of C1-3 alkyl, C3-6cycloalkyl and phenyl.

[0302] Even much more preferred compounds of the formula (Ia) are thosewherein:

[0303] R₁ is C5-6 cycloalkyl, phenyl, naphthyl, piperidinyl,morpholinyl, piperazinyl, furanyl, thienyl, pyrrolyl, pyranyl,thiopyranyl or amino wherein R₁ is optionally substituted by one or moreR_(b);

[0304] R_(b) is selected from the group consisting of C1-3 alkyl, C5-6cycloalkyl, phenyl, furanyl, thienyl, pyrrolyl, imidazolyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,C1-3 alkoxy, C1-3 alkoxycarbonyl, carbamoyl wherein the nitrogen atommay be independently mono or di-substituted by C1-3 alkyl or phenyl;C1-5 alkanoylamino, aroylamino, ureido wherein either nitrogen atom maybe independently substituted by C1-3alkyl or phenyl; C1-5alkylsulfonylamino, arylsulfonylamino, amino wherein the nitrogen atommay be independently mono or di-substituted by C1-3alkyl or phenyl;halogen, hydroxy, oxo, carboxy and cyano, R_(b) may be furtheroptionally substituted by one or more R_(c);

[0305] R_(d) is selected from the group consisting of C1-3 alkyl, C1-3alkoxy, halogen and hydroxy;

[0306] R_(d) is selected from the group consisting of C1-3 alkyl, C3-6cycloalkyl, phenyl, naphthyl, 4-piperidinyl, furanyl, thienyl,thiazolyl, imidazolyl, pyridinyl, indolyl, C1-3alkoxy,C1-5alkoxycarbonyl, C1-5alkanoyloxy, benzoyloxy, carbamoyl wherein thenitrogen atom may be independently mono or di-substituted by C1-3alkylor phenyl; C1-5alkanoylamino, C1-3 alkylthio wherein the sulfur atom maybe oxidized to a sulfoxide or sulfone, C1-3alkoxycarbonylamino,C1-3alkylsulfonylamino, amino wherein the nitrogen atom may beindependently mono or di-substituted by C1-3 alkyl or phenyl, halogen,hydroxy, oxo, carboxy and cyano, R_(d) may be further optionallysubstituted by one or more R_(e);

[0307] R_(e) is selected from the group consisting of C1-3 alkyl,phenyl, benzyl, C1-3 alkoxy, phenoxy, benzyloxy, benzoyl, halogen,hydroxy, oxo, carboxy and cyano;

[0308] R₅ is H or methyl;

[0309] R₆ is C1-5 alkyl or phenyl, wherein R₆ is optionally substitutedby one or more groups of the formula R_(f),

[0310] R_(f) is selected from the group consisting of methyl, C3-6cycloalkyl, phenyl, naphthyl, furanyl, thienyl, thiazolyl, imidazolyl,pyridinyl, indolyl, C1-3 alkoxy, benzyloxy, C1-5 alkanoylamino,aroylamino, methylthio wherein the sulfur atom may be oxidized to asulfoxide or sulfone, benzylthio wherein the sulfur atom may be oxidizedto a sulfoxide or sulfone, C1-3 alkoxycarbonylamino, amino wherein thenitrogen atom may be independently mono or di-substituted by C1-5 alkylor phenyl; halogen, hydroxy, oxo, carboxy and cyano, R_(f) may befurther optionally substituted by one or more R_(g);

[0311] R_(g) is selected from the group consisting of C1-3 alkyl, phenyloptionally substituted by halogen or methyl; C1-3 alkoxy, aryloxy,benzyloxy, C1-3 alkoxycarbonyl, carbamoyl wherein the nitrogen atom maybe independently mono or di-substituted by C1-3 alkyl or phenyl; C1-5alkanoylamino, aroylamino, amino wherein the nitrogen atom may beindependently mono or di-substituted by C1-3 alkyl or phenyl; halogen,hydroxy, oxo, carboxy and cyano;

[0312] R_(h) is selected from the group consisting of C1-3 alkyl,phenyl, C1-3 alkoxycarbonyl, benzyloxy and carboxy;

[0313] R₈ is a heteroaryl ring selected from the group consisting ofoxazolyl, thiazolyl, imidazolyl, pyrazolyl, pyridyl, benzimidazolyl,benzthiazolyl and benzoxazolyl, wherein any of the above R8 can beoptionally substituted by one or more R_(j);

[0314] R_(j) is selected from the group consisting of C1-5 alkyl,cyclohexyl, phenyl, piperidinyl, furanyl, thienyl, pyridinyl, benzyl,methoxy, phenoxy, benzyloxy, methoxycarbonyl, acetyloxy, benzoyloxy,carbamoyl wherein the nitrogen atom may be independantly mono ordi-susbstituted by methyl, phenyl, furanyl, thienyl; acetylamino,benzoylamino, ureido wherein either nitrogen atom may be independentlysubstituted by methyl or phenyl; methoxycarbonylamino, C1-3alkylsulfonylamino, arylsulfonylamino, amino wherein the nitrogen atommay be independently mono or di-susbstituted by methyl, phenyl, furanylor thienyl; halogen, hydroxy, carboxy and cyano, R_(j) may be furtheroptionally substituted by one or more R_(k);

[0315] R_(k) is selected from the group consisting of methyl, C5-6cycloalkyl, phenyl, piperidinyl, piperazinyl, furanyl, thienyl, C1-3alkoxy, phenoxy, benzyloxy, methoxycarbonyl, acetyloxy, benzoyloxy,carbamoyl wherein the nitrogen atom may be independantly mono ordi-susbstituted by methyl or phenyl; acetylamino, benzoylamino, ureidowherein either nitrogen atom may be independently substituted by methylor phenyl; benzyloxycarbonylamino, benzyloxycarbonylamino C1-5alkyl,amino wherein the nitrogen atom may be independently mono ordi-susbstituted by C1-3 alkyl, phenyl, furanyl, or thienyl; halogen,hydroxy, carboxy, cyano and nitro, wherein R_(k) may be furtheroptionally substituted by R1;

[0316] R₁ is selected from the group consisting of methyl, C3-6cycloalkyl and phenyl.

[0317] Yet even more preferred compounds of the formula (Ia) are thosewherein:

[0318] A is —C(O)— or —SO₂—;

[0319] R₁ is cyclohexyl, phenyl, naphthyl, piperidinyl, morpholinyl,piperazinyl, pyranyl, thiopyranyl or amino, wherein R1 is optionallysubstituted by one or more R_(b);

[0320] R_(b) is selected from the group consisting of C1-3 alkyl, C5-6cycloalkyl, phenyl, furanyl, thienyl, pyrrolyl, imidazolyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,C1-3 alkoxy, C1-3 alkoxycarbonyl, carbamoyl wherein the nitrogen atommay be independently mono or di-substituted by C1-3 alkyl or phenyl;C1-5 alkanoylamino, aroylamino, C1-5 alkylsulfonylamino,arylsulfonylamino, amino wherein the nitrogen atom may be independentlymono or di-substituted by C1-3 alkyl; halogen, hydroxy, oxo, carboxy andcyano, R_(b) may be further optionally substituted by one or more R_(c);

[0321] R_(c) is selected from the group consisting of C1-3 alkoxy,halogen and hydroxy;

[0322] R₃ is C1-5 alkyl or C5-6 cycloalkyl, wherein R₃ is optionallysubstituted by one or more R_(d);

[0323] R_(d) is selected from the group consisting of methyl, C3-6cycloalkyl, phenyl, thienyl, imidazolyl, pyridinyl, indolyl, C1-4alkoxy, C1-5 alkanoylamino, methylthio wherein the sulfur atom may beoxidized to a sulfoxide or sulfone, halogen, hydroxy, oxo, carboxy andcyano, R_(d) may be further optionally substituted by one or more R_(e);

[0324] R_(e) is selected from the group consisting of methyl, phenyl,benzyl, methoxy, phenoxy, benzyloxy, benzoyl, halogen and hydroxy;

[0325] R_(f) is selected from the group consisting of C3-6 cycloalkyl,phenyl, naphthyl, thienyl, imidazolyl, pyridinyl, indolyl, methoxy,benzyloxy, C1-3 alkanoylamino, methylthio wherein the sulfur atom may beoxidized to a sulfoxide or sulfone, benzylthio wherein the sulfur atommay be oxidized to a sulfoxide or sulfone, methoxycarbonylamino, aminowherein the nitrogen atom may be independently mono or di-substituted byC1-3 alkyl; halogen, hydroxy, carboxy and cyano, R_(f) may be furtheroptionally substituted by one or more R_(g);

[0326] R_(g) is selected from the group consisting of methyl, phenyloptionally substituted by halogen or methyl; methoxy, phenoxy,benzyloxy, methoxycarbonyl, amino wherein the nitrogen atom may beindependently mono or di-substituted by C1-3 alkyl or phenyl; halogen,hydroxy and carboxy;

[0327] R₈ is a heteroaryl ring selected from the group consisting ofoxazolyl, thiazolyl, imidazolyl, pyridyl, benzthiazolyl andbenzoxazolyl, wherein any of the above R₈ can be optionally substitutedby one or more R_(j);

[0328] R_(j) is selected from the group consisting of C1-5 alkyl,phenyl, furanyl, thienyl, piperidinyl, pyridinyl, benzyl, methoxy,methoxycarbonyl, acetyloxy, benzoyloxy, carbamoyl wherein the nitrogenatom may be independantly mono or di-susbstituted by methyl or phenyl;acetylamino, benzoylamino, ureido wherein either nitrogen atom may beindependently substituted by methyl or phenyl; methoxycarbonylamino,amino wherein the nitrogen atom may be independently mono ordi-susbstituted by methyl, phenyl; halogen, hydroxy, carboxy and cyano,R_(j) may be further optionally substituted by one or more R_(k); and

[0329] R_(k) is selected from the group consisting of methyl, C5-6cycloalkyl, phenyl, piperidinyl, methoxy, phenoxy, benzyloxy,methoxycarbonyl, carbamoyl wherein the nitrogen atom may beindependantly mono or di-susbstituted by methyl or phenyl; ureidowherein either nitrogen atom may be independently substituted by methylor phenyl; benzyloxycarbonylamino, benzyloxycarbonylaminoC1-5 alkyl,amino wherein the nitrogen atom may be independently mono ordi-susbstituted by C1-3alkyl, phenyl, furanyl and thienyl; halogen,hydroxy, carboxy, cyano and nitro, wherein R_(k) may be furtheroptionally substituted by R₁;

[0330] R₁ is selected from the group consisting of methyl and phenyl.

[0331] Penultimately preferred compounds of the formula (Ia) are thosewherein:

[0332] R₁ is cyclohexyl, phenyl, naphthyl, piperidinyl, morpholinyl,piperazinyl, pyranyl or thiopyranyl, wherein R₁ is optionallysubstituted by one or more R_(b);

[0333] R_(b) is selected from the group consisting of, pyrrolyl,imidazolyl, indolyl, benzimidazolyl, methoxy, methoxycarbonyl, aminowherein the nitrogen atom may be independently mono or di-substituted byC1-3 alkyl; halogen, hydroxy and carboxy, R_(b) may be furtheroptionally substituted by one or more R_(e);

[0334] R_(e) is selected from the group consisting of methoxy, halogenand hydroxy;

[0335] R_(d) is selected from the group consisting of methyl, C3-6cycloalkyl, phenyl, C1-4 alkoxy, C1-3 alkanoylamino, methylthio whereinthe sulfur atom may be oxidized to a sulfoxide or sulfone, halogen,hydroxy, oxo, carboxy and cyano, R_(d) may be further optionallysubstituted by one or more R_(e);

[0336] R_(e) is selected from the group consisting of methyl, phenyl,methoxy, halogen and hydroxy;

[0337] R₅ is H;

[0338] R_(f) is selected from the group consisting of C5-6 cycloalkyl,phenyl, naphthyl, thienyl, indolyl, methoxy, methylthio wherein thesulfur atom may be oxidized to a sulfoxide or sulfone,methoxycarbonylamino, halogen, hydroxy, carboxy and cyano, R_(f) may befurther optionally substituted by one or more R_(g);

[0339] R_(g) is selected from the group consisting of methyl, phenyloptionally substituted by halogen; methoxy, phenoxy, benzyloxy,methoxycarbonyl, halogen, hydroxy and carboxy;

[0340] R₈ is a heteroaryl ring selected from the group consisting ofoxazolyl, thiazolyl, pyridyl, benzthiazolyl and benzoxazolyl, whereinany of the above R₈ can be optionally substituted by one or more R_(j);

[0341] R_(j) is selected from the group consisting of C1-5 alkyl,phenyl, piperidinyl, pyridinyl, benzyl, methoxy, methoxycarbonyl,acetyloxy, benzoyloxy, carbamoyl wherein the nitrogen atom may beindependantly mono or di-susbstituted by methyl or phenyl;methoxycarbonylamino, halogen, hydroxy and carboxy, R_(j) may be furtheroptionally substituted by one or more R_(k);

[0342] R_(k) is selected from the group consisting of methyl, C5-6cycloalkyl, phenyl, piperidinyl, methoxy, methoxycarbonyl, carbamoylwherein the nitrogen atom may be independantly mono or di-susbstitutedby methyl or phenyl; benzyloxycarbonylamino, amino wherein the nitrogenatom may be independently mono or di-susbstituted by methyl or phenyl;halogen, hydroxy and carboxy.

[0343] Ultimately preferred compounds of the formula (Ia) are thosewherein:

[0344] R₁ is phenyl or 4-morpholinyl, wherein R₁ is optionallysubstituted by one or more R_(b);

[0345] R_(b) is selected from the group consisting of benzimidazolyl,methoxy and dimethylamino, R_(b) may be further optionally substitutedby a halogen atom;

[0346] R₃ is C1-5 alkyl wherein R₃ is optionally substituted by one ormore R_(d);

[0347] R_(d) is selected from the group consisting of C3-6 cycloalkyland phenyl, R_(d) may be further optionally substituted by one or moreR_(e);

[0348] R_(e) is selected from the group consisting of methyl andhalogen;

[0349] R₆ is C1-5 alkyl optionally substituted by one or more R_(f);

[0350] R_(f) is selected from the group consisting of C5-6 cycloalkyl,phenyl, methylthio wherein the sulfur atom may be oxidized to asulfoxide or sulfone, and halogen, R_(f) may be further optionallysubstituted by one or more R_(g);

[0351] R_(g) is selected from the group consisting of methyl, methoxy,methoxycarbonyl, halogen and hydroxy;

[0352] R₈ is a heteroaryl ring selected from the group consisting ofoxazolyl, pyridyl, benzthiazolyl and benzoxazolyl, wherein any of theabove R₈ can be optionally substituted by one or more R_(j);

[0353] R_(j) is selected from the group consisting of C1-5 alkyl,phenyl, pyridinyl, piperidinyl, methoxycarbonyl, carbamoyl wherein thenitrogen atom may be independantly mono or disubstituted by methyl orphenyl; methoxycarbonylamino and halogen, R_(j) may be furtheroptionally substituted by one or more R_(k);

[0354] R_(k) is selected from the group consisting of methyl, C5-6cycloalkyl, phenyl, methoxycarbonyl, carbamoyl, benzyloxycarbonylaminoand halogen.

[0355] The invention also provides novel compounds of the formula (II):

[0356] wherein:

[0357] A is —C(Y)— or —SO₂—

[0358] Y is O, S or NR_(a) wherein R_(a) is selected from the groupconsisting of H, alkyl, aryl, alkoxy, aryloxy, alkylamino and arylamino;

[0359] R₁ is alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl or aminowherein R₁ is optionally substituted by one or more R_(b);

[0360] R_(b) is selected from the group consisting of alkyl, cycloalkyl,aryl, heterocyclyl, heteroaryl, alkoxy, aryloxy, alkanoyl, aroyl,alkoxycarbonyl, aryloxycarbonyl, alkanoyloxy, aroyloxy, carbamoylwherein the nitrogen atom may be independently mono or di-substituted byalkyl, aryl, heterocyclyl or heteroaryl, alkanoylamino, aroylamino,alkylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, arylthio wherein the sulfur atom may be oxidized to a sulfoxideor sulfone, ureido wherein either nitrogen atom may be independentlysubstituted by alkyl, aryl, heterocyclyl or heteroaryl,alkoxycarbonylamino, aryloxycarbonylamino, alkylcarbamoyloxy,arylcarbamoyloxy, alkylsulfonylamino, arylsulfonylamino,alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atommay be independently mono or di-substituted by alkyl, aryl, heterocyclylor heteroaryl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino andguanidino; R_(b) may be further optionally substituted by one or moreR_(c);

[0361] R_(c) is selected from the group consisting of alkyl, cycloalkyl,aryl, heterocyclyl, heteroaryl, arylalkyl, alkoxy, aryloxy, arylalkoxy,alkanoyl, aroyl, amino wherein the nitrogen atom may be independentlymono or di-substituted by alkyl, aryl, heterocyclyl or heteroaryl,halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino;

[0362] R₂ is H or alkyl;

[0363] R₃ is H, alkyl, cycloalkyl, aryl, heterocyclyl or heteroaryl,wherein R₃ is optionally substituted by one or more R_(d);

[0364] R_(d) is selected from the group consisting of alkyl, cycloalkyl,aryl, heterocyclyl, heteroaryl, alkoxy, aryloxy, arylalkoxy,alkoxycarbonyl, aryloxycarbonyl, alkanoyl, aroyl, alkanoyloxy, aroyloxy,carbamoyl wherein the nitrogen atom may be independently mono ordi-substituted by alkyl, aryl, heterocyclyl or heteroaryl,alkanoylamino, aroylamino, alkylthio wherein the sulfur atom may beoxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom maybe oxidized to a sulfoxide or sulfone, ureido wherein either nitrogenatom may be independently substituted by alkyl, aryl, heterocyclyl orheteroaryl, alkoxycarbonylamino, aryloxycarbonylamino,alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino,arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino whereinthe nitrogen atom may be independently mono or di-substituted by alkyl,aryl, heterocyclyl or heteroaryl, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino, R_(d) may be further optionallysubstituted by one or more R_(e);

[0365] R_(e) is selected from the group consisting of alkyl, cycloalkyl,aryl, arylalkyl, alkoxy, aryloxy, arylalkoxy, alkanoyl, aroyl, amino,halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino;

[0366] R₄ is H or alkyl;

[0367] R₅ is H or alkyl;

[0368] R₆ is H, alkyl, cycloalkyl, aryl, heterocyclyl, aryl, heteroarylor cyano, wherein R₆ is optionally substituted by one or more R_(f);

[0369] R_(f) is selected from the group consisting of alkyl, cycloalkyl,aryl, heterocyclyl, heteroaryl, alkoxy, aryloxy, arylalkoxy, alkanoyl,aroyl, alkoxycarbonyl, aryloxycarbonyl, alkanoyloxy, aroyloxy,heteroarylalkoxy, carbamoyl wherein the nitrogen atom may beindependently mono or di-substituted by alkyl, aryl, heterocyclyl orheteroaryl, alkanoylamino, aroylamino, alkylcarbamoyl, arylcarbamoyl,alkylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, arylthio wherein the sulfur atom may be oxidized to a sulfoxideor sulfone, arylalkylthio wherein the sulfur atom may be oxidized to asulfoxide or sulfone, ureido wherein either nitrogen atom may beindependently substituted by alkyl, aryl, heterocyclyl or heteroaryl,alkoxycarbonylamino, aryloxycarbonylamino, alkylcarbamoyloxy,arylcarbamoyloxy, alkylsulfonylamino, arylsulfonylamino,alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atommay be independently mono or di-substituted by alkyl, aryl, heterocyclylor heteroaryl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino andguanidino, R_(f) may be further optionally substituted by one or moreR_(g);

[0370] R_(g) is selected from the group consisting of alkyl, cycloalkyl,aryl optionally substituted by one or more groups selected from halogen,methyl or methoxy, heterocyclyl, heteroaryl, alkoxy, aryloxy,arylalkoxy, alkoxycarbonyl, aryloxycarbonyl, alkanoyloxy, aroyloxy,carbamoyl wherein the nitrogen atom may be independently mono ordi-substituted by alkyl, aryl, heterocyclyl or heteroaryl,alkanoylamino, aroylamino, alkylcarbamoyl, arylcarbamoyl, alkylthiowherein the sulfur atom may be oxidized to a sulfoxide or sulfone,arylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, ureido wherein either nitrogen atom may be independentlysubstituted by alkyl, aryl, heterocyclyl or heteroaryl,alkoxycarbonylamino, aryloxycarbonylamino, alkylcarbamoyloxy,arylcarbamoyloxy, alkylsulfonylamino, arylsulfonylamino,alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atommay be independently mono or di-substituted by alkyl, aryl, heterocyclylor heteroaryl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino andguanidino;

[0371] or R₅ together with R₆ form a 3 to 6 membered carbocyclic ring,the carbocyclic ring being optionally substituted with one or moreR_(h);

[0372] R_(h) is selected from the group consisting of alkyl, aryl,alkoxycarbonyl, aryloxycarbonyl, arylalkoxycarbonyl, carbamoyl whereinthe nitrogen atom may be optionally mono or di-substituted with a groupselected from alkyl, cycloalkyl, aryl, arylalkyl, heterocyclyl,heteroaryl, halogen, hydroxy, carboxy and cyano;

[0373] X is O, S or N—OH;

[0374] with the proviso that when Y is O and R₆ is arylalkyl orheteroarylalkyl then R₁ cannot be alkyl, cycloalkyl, aryl, heteroaryl,cycloalkyl-alkyl, aryl-alkyl or aryl-cycloalkyl.

[0375] Preferred compounds of the formula (II) are those wherein:

[0376] Y is O, S or NR_(a) wherein R_(a) is H, alkyl or aryl;

[0377] R₁ is C1-8alkyl, C3-7cycloalkyl, aryl, heterocyclyl selected fromthe group consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl, indolinyl, pyranyl and thiopyranyl,heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl, phenoxazinyl, and amino wherein R1 is optionallysubstituted by one or more R_(b);

[0378] R_(b) is selected from the group consisting of C1-8 alkyl, C3-7cycloalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl, heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl,isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl,thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl,isoindolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl or phenoxazinyl, C1-8 alkoxy, aryloxy, C1-8alkoxycarbonyl, aryloxycarbonyl, C1-8 alkanoyloxy, aroyloxy, carbamoylwherein the nitrogen atom may be independently mono or di-substituted byC1-8 alkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl, or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl,isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl,thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl,isoindolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, C1-8 alkanoylamino,aroylamino, C1-8 alkylthio wherein the sulfur atom may be oxidized to asulfoxide or sulfone, arylthio wherein the sulfur atom may be oxidizedto a sulfoxide or sulfone, ureido wherein either nitrogen atom may beindependently substituted by alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl, or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, purinyl, quinolinyl, isoquinolinyl,quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyl or phenoxazinyl,alkoxycarbonylamino, aryloxycarbonylamino, alkylcarbamoyloxy,arylcarbamoyloxy, alkylsulfonylamino, arylsulfonylamino,alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atommay be independently mono or di-substituted by alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, pyrazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl and phenoxazinyl, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino, guanidino; R_(b) may be further optionally substitutedby one or more R_(c);

[0379] R_(c) is selected from the group consisting of C1-8 alkyl, C3-6cycloalkyl, aryl, C1-8 alkoxy, aryloxy, halogen, hydroxy, oxo, carboxy,cyano, nitro, amidino and guanidino;

[0380] R₃ is H, C1-8 alkyl, C3-7 cycloalkyl, aryl wherein R₃ isoptionally substituted by one or more R_(d);

[0381] R_(d) is selected from the group consisting of C1-8 alkyl, C3-7cycloalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl,isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl,thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl,isoindolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, C1-8 alkoxy, aryloxy,alkanoyl, aroyl, C1-8 alkoxycarbonyl, aryloxycarbonyl, C1-8 alkanoyloxy,aroyloxy, carbamoyl wherein the nitrogen atom may be independently monoor di-substituted by C1-8 alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl, or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, purinyl, quinolinyl, isoquinolinyl,quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyl and phenoxazinyl,C1-8 alkanoylamino, aroylamino, C1-8 alkylthio wherein the sulfur atommay be oxidized to a sulfoxide or sulfone, arylthio wherein the sulfuratom may be oxidized to a sulfoxide or sulfone, ureido wherein eithernitrogen atom may be independently substituted by alkyl, aryl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl and phenoxazinyl, alkoxycarbonylamino,aryloxycarbonylamino, alkylcarbamoyloxy, arylcarbamoyloxy,alkylsulfonylamino, arylsulfonylamino, alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom may be independentlymono or di-substituted by alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, purinyl, quinolinyl, isoquinolinyl,quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyl and phenoxazinyl,halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino, guanidino, R_(d)may be further optionally substituted by one or more R_(e);

[0382] R_(e) is selected from the group consisting of C1-8 alkyl, C3-6cycloalkyl, aryl, arylalkyl, C1-8 alkoxy, aryloxy, arylalkoxy, aroyl,amino, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino andguanidino;

[0383] R₆ is H, C1-8 alkyl, C3-7 cycloalkyl, aryl or cyano, wherein R₆is optionally substituted by one or more R_(f);

[0384] R_(f) is selected from the group consisting of C1-8 alkyl, C3-7cycloalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl,isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl,thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl,isoindolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, C1-8 alkoxy, aryloxy,arylC1-8alkoxy, heteroarylC1-8alkoxy, C1-8 alkoxycarbonyl,aryloxycarbonyl, C1-8 alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom may be independently mono or di-substituted by C1-8 alkyl,aryl, heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl and phenoxazinyl, C1-8 alkanoylamino, aroylamino, C1-8alkylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, arylthio wherein the sulfur atom may be oxidized to a sulfoxideor sulfone, arylC1-8 alkylthio wherein the sulfur atom may be oxidizedto a sulfoxide or sulfone, ureido wherein either nitrogen atom may beindependently substituted by alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl, or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, purinyl, quinolinyl, isoquinolinyl,quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyl and phenoxazinyl,alkoxycarbonylamino, aryloxycarbonylamino, alkylcarbamoyloxy,arylcarbamoyloxy, alkylsulfonylamino, arylsulfonylamino,alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atommay be independently mono or di-substituted by alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl,oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyridinyl,pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidinoand guanidino, R_(f) may be further optionally substituted by one ormore R_(g);

[0385] R_(g) is selected from the group consisting of C1-8 alkyl, C3-7cycloalkyl, aryl optionally substituted by one or more groups selectedfrom halogen, methyl or methoxy, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl; heteroaryl selected from the group consistingof furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl,pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl,thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl,isoindolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, C1-8 alkoxy, aryloxy,arylC1-8alkoxy, C1-8 alkoxycarbonyl, aryloxycarbonyl, C1-8 alkanoyloxy,aroyloxy, carbamoyl wherein the nitrogen atom may be independently monoor di-substituted by C1-8 alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl, or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, purinyl, quinolinyl, isoquinolinyl,quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyl and phenoxazinyl,C1-8 alkanoylamino, aroylamino, C1-8 alkylthio wherein the sulfur atommay be oxidized to a sulfoxide or sulfone, arylthio wherein the sulfuratom may be oxidized to a sulfoxide or sulfone, ureido wherein eithernitrogen atom may be independently substituted by alkyl, aryl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl and phenoxazinyl, alkoxycarbonylamino,aryloxycarbonylamino, alkylcarbamoyloxy, arylcarbamoyloxy,alkylsulfonylamino, arylsulfonylamino, alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom may be independentlymono or di-substituted by alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl, or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, purinyl, quinolinyl, isoquinolinyl,quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyl and phenoxazinyl,halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino, and guanidino;

[0386] R_(h) is selected from the group consisting of C1-8 alkyl, aryl,C1-8 alkoxycarbonyl, aryloxycarbonyl, arylC1-8alkoxycarbonyl, carbamoylwherein the nitrogen atom may be optionally mono or di-substituted witha group selected from C1-8 alkyl, C3-7 cycloalkyl, aryl, arylC1-8alkyl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl and phenoxazinyl, halogen, hydroxy, carboxy, and cyano;and

[0387] X is O or S.

[0388] More preferred compounds of the formula (II) are those wherein:

[0389] Y is O or S;

[0390] R₁ is C1-5 alkyl, C3-7 cycloalkyl, phenyl, naphthyl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl, indolinyl, pyranyl andthiopyranyl, heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl,tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl or amino; wherein R1 is optionallysubstituted by one or more R_(b);

[0391] R_(b) is selected from the group consisting of C1-5 alkyl, C3-7cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl;, heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,quinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl, C1-5 alkoxy,aryloxy, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy,aroyloxy, carbamoyl wherein the nitrogen atom may be independently monoor di-substituted by C1-8 alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl, or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,quinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl, C1-5alkanoylamino, aroylamino, C1-5 alkylthio wherein the sulfur atom may beoxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom maybe oxidized to a sulfoxide or sulfone, ureido wherein either nitrogenatom may be independently substituted by alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl,pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, quinolinyl, isoquinolinyl, quinazolinyland quinoxalinyl, C1-5 alkoxycarbonylamino, aryloxycarbonylamino, C1-5alkylcarbamoyloxy, arylcarbamoyloxy, C1-5 alkylsulfonylamino,arylsulfonylamino, C1-5 alkylaminosulfonyl, arylaminosulfonyl, aminowherein the nitrogen atom may be independently mono or di-substituted byalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl, or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl,tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino, R_(b) may be further optionallysubstituted by one or more R_(c);

[0392] R_(c) is selected from the group consisting of C1-5 alkyl, C3-6cycloalkyl, aryl, C1-5 alkoxy, aryloxy, halogen, hydroxy, oxo, carboxy,cyano, nitro, amidino and guanidino;

[0393] R₂ is H or C1-3 alkyl;

[0394] R₃ is H, C1-5 alkyl, C3-7 cycloalkyl, aryl wherein R₃ isoptionally substituted by one or more R_(d);

[0395] R_(d) is selected from the group consisting of C1-5 alkyl, C3-7cycloalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl,tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, C1-5 alkoxy, aryloxy, C1-5alkanoyl,aroyl, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy,carbamoyl wherein the nitrogen atom may be independently mono ordi-substituted by C1-5 alkyl, aryl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl, or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,quinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl, C1-5alkanoylamino, aroylamino, C1-5 alkylthio wherein the sulfur atom may beoxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom maybe oxidized to a sulfoxide or sulfone, ureido wherein either nitrogenatom may be independently substituted by C1-5 alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, or heteroarylselected the group consisting of furanyl, thienyl, pyrrolyl, oxazolyl,thiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl,pyrazinyl, indolyl, benzofuranyl, benzothienyl, benzimidazolyl,benzthiazolyl, quinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl,C1-5 alkoxycarbonylamino, aryloxycarbonylamino, C1-5 alkylcarbamoyloxy,arylcarbamoyloxy, C1-5 alkylsulfonylamino, arylsulfonylamino, C1-5alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atommay be independently mono or di-substituted by C1-5 alkyl, aryl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl,pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, quinolinyl, isoquinolinyl, quinazolinyland quinoxalinyl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidinoand guanidino, R_(d) may be further optionally substituted by one ormore R_(e);

[0396] R_(e) is selected from the group consisting of C1-5 alkyl, C3-6cycloalkyl, aryl, arylalkyl, C1-5 alkoxy, aryloxy, arylC1-5alkoxy,aroyl, amino, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino andguanidino;

[0397] R₄ is H or C1-3 alkyl

[0398] R₅ is H or C1-8 alkyl

[0399] R₆ is H, C1-5 alkyl, C3-7 cycloalkyl, aryl or cyano, wherein R₆is optionally substituted by one or more R_(f);

[0400] R_(f) is selected from the group consisting of C1-5 alkyl, C3-7cycloalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl,tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, C1-5 alkoxy, aryloxy, arylC1-5alkoxy,heteroarylC1-5alkoxy, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom may beindependently mono or di-substituted by C1-5 alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl,pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, quinolinyl, isoquinolinyl, quinazolinyland quinoxalinyl, C1-5 alkanoylamino, aroylamino, C1-5 alkylthio whereinthe sulfur atom may be oxidized to a sulfoxide or sulfone, arylthiowherein the sulfur atom may be oxidized to a sulfoxide or sulfone,arylC1-5 alkylthio wherein the sulfur atom may be oxidized to asulfoxide or sulfone, ureido wherein either nitrogen atom may beindependently substituted by C1-5 alkyl, aryl, heterocyclyl selectedfrom the group consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,quinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl, C1-5alkoxycarbonylamino, aryloxycarbonylamino, C1-5 alkylcarbamoyloxy,arylcarbamoyloxy, C1-5 alkylsulfonylamino, arylsulfonylamino, C1-5alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atommay be independently mono or di-substituted by C1-5 alkyl, aryl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl,pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, quinolinyl, isoquinolinyl, quinazolinyland quinoxalinyl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidinoand guanidino, R_(f) may be further optionally substituted by one ormore R_(g);

[0401] R_(g) is selected from the group consisting of C1-5 alkyl, C3-7cycloalkyl, aryl optionally substituted by one or more groups selectedfrom halogen, methyl or methoxy, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl, heteroaryl selected from the group consistingof furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl,triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, quinolinyl,isoquinolinyl, quinazolinyl and quinoxalinyl, C1-5 alkoxy, aryloxy,arylC1-5alkoxy, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy,aroyloxy, carbamoyl wherein the nitrogen atom may be independently monoor di-substituted by C1-5 alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,quinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl, C1-5alkanoylamino, aroylamino, C1-5 alkylthio wherein the sulfur atom may beoxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom maybe oxidized to a sulfoxide or sulfone, ureido wherein either nitrogenatom may be independently substituted by C1-5 alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl,pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, quinolinyl, isoquinolinyl, quinazolinyland quinoxalinyl, C1-5 alkoxycarbonylamino, aryloxycarbonylamino, C1-5alkylcarbamoyloxy, arylcarbamoyloxy, C1-5 alkylsulfonylamino,arylsulfonylamino, C1-5 alkylaminosulfonyl, arylaminosulfonyl, aminowherein the nitrogen atom may be independently mono or di-substituted byC1-5 alkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl, or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl,tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino;

[0402] R_(h) is selected from the group consisting of C1-5 alkyl, aryl,C1-5 alkoxycarbonyl, aryloxycarbonyl, arylC1-5alkoxycarbonyl, carbamoylwherein the nitrogen atom may be optionally mono or di-substituted witha group selected from C1-5 alkyl, C3-7 cycloalkyl, aryl, arylC1-5alkyl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl,pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, quinolinyl, isoquinolinyl, quinazolinyland quinoxalinyl, halogen, hydroxy, carboxy and cyano.

[0403] Even more preferred compounds of the formula (II) are thosewherein:

[0404] Y is O;

[0405] R₁ is C1-5 alkyl, C3-7 cycloalkyl, phenyl, naphthyl, heterocyclylselected from the group consisting of piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl, pyranyl and thiopyranyl; heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, quinolinyl andisoquinolinyl; or amino wherein R₁ is optionally substituted by one ormore R_(b);

[0406] R_(b) is selected from the group consisting of C1-5 alkyl, C3-7cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl; heteroaryl selected from the group consistingof furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl,tetrazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, quinolinyl and isoquinolinyl, C1-5alkoxy, aryloxy, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy,aroyloxy, carbamoyl wherein the nitrogen atom may be independently monoor di-substituted by C1-5 alkyl, phenyl, naphthyl, heterocyclyl selectedfrom the group consisting of pyrrolidinyl, piperidinyl, morpholinyl,piperazinyl and indolinyl, or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, tetrazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, quinolinyl and isoquinolinyl, C1-5alkanoylamino, aroylamino, C1-5 alkylthio wherein the sulfur atom may beoxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom maybe oxidized to a sulfoxide or sulfone, ureido wherein either nitrogenatom may be independently substituted by alkyl or aryl, C1-5alkoxycarbonylamino, aryloxycarbonylamino, C1-5 alkylcarbamoyloxy,arylcarbamoyloxy, C1-5 alkylsulfonylamino, arylsulfonylamino, C1-5alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atommay be independently mono or di-substituted by alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, quinolinyl andisoquinolinyl, halogen, hydroxy, oxo, carboxy, cyano and nitro, R_(b)may be further optionally substituted by one or more R_(e);

[0407] R_(c) is selected from the group consisting of C1-5 alkyl, C3-6cycloalkyl, aryl, C1-5 alkoxy, aryloxy, halogen, hydroxy, oxo, carboxyand cyano;

[0408] R₂ is H or methyl;

[0409] R₃ is H, C11-5 alkyl, C3-7 cycloalkyl or phenyl wherein R₃ isoptionally substituted by one or more R_(d);

[0410] R_(d) is selected from the group consisting of C1-3 alkyl, C3-6cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of piperidinyl, morpholinyl and piperazinyl, heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, quinolinyl andisoquinolinyl, C1-5 alkoxy, aryloxy, aroyl, C1-5 alkoxycarbonyl,aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom may be independently mono or di-substituted by C1-5 alkyl,aryl, heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl and piperazinyl or heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, quinolinyl and isoquinolinyl, C1-5alkanoylamino, aroylamino, C1-5 alkylthio wherein the sulfur atom may beoxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom maybe oxidized to a sulfoxide or sulfone, ureido wherein either nitrogenatom may be independently substituted by C1-5 alkyl, phenyl, naphthyl,heterocyclyl selected from the group consisting of piperidinyl,morpholinyl and piperazinyl or heteroaryl selected the group consistingof furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl,pyridinyl, indolyl, benzofuranyl, benzothienyl, benzimidazolyl,benzthiazolyl, quinolinyl and isoquinolinyl, C1-5 alkoxycarbonylamino,aryloxycarbonylamino, C1-5 alkylcarbamoyloxy, arylcarbamoyloxy, C1-5alkylsulfonylamino, arylsulfonylamino, C1-5 alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom may be independentlymono or di-substituted by C1-5 alkyl, phenyl, naphthyl, heterocyclylselected from the group consisting of piperidinyl, morpholinyl andpiperazinyl or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, quinolinyland isoquinolinyl, halogen, hydroxy, oxo, carboxy and cyano, R_(d) maybe further optionally substituted by one or more R_(e);.

[0411] R_(e) is selected from the group consisting of C1-5 alkyl, C3-6cycloalkyl, aryl, arylC1-5alkyl, C1-5 alkoxy, aryloxy, arylC1-3alkoxy,aroyl, amino, halogen, hydroxy, oxo, carboxy and cyano;

[0412] R₄ is H or methyl;

[0413] R₅ is H or C1-5 alkyl;

[0414] R₆ is H, C1-5 alkyl, C3-7 cycloalkyl, phenyl, naphthyl or cyano,wherein R₆ is optionally substituted by one or more R_(f);.

[0415] R_(f) is selected from the group consisting of C1-5 alkyl, C3-7cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl; heteroaryl selected from the group consistingof furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl,triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, quinolinyl,isoquinolinyl, quinazolinyl and quinoxalinyl, C1-5 alkoxy, aryloxy,arylC1-5alkoxy, heteroarylC1-5alkoxy, C1-5 alkoxycarbonyl,aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom may be independently mono or di-substituted by C1-5 alkyl,aryl, heterocyclyl selected from the group consisting of piperidinyl,morpholinyl and piperazinyl or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, quinolinyl and isoquinolinyl, C1-5alkanoylamino, aroylamino, C1-5 alkylthio wherein the sulfur atom may beoxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom maybe oxidized to a sulfoxide or sulfone, arylC1-5 alkylthio wherein thesulfur atom may be oxidized to a sulfoxide or sulfone, ureido whereineither nitrogen atom may be independently substituted by C1-5 alkyl,aryl, heterocyclyl selected from the group consisting of piperidinyl,morpholinyl and piperazinyl or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, quinolinyl and isoquinolinyl, C1-5alkoxycarbonylamino, aryloxycarbonylamino, C1-5 alkylcarbamoyloxy,arylcarbamoyloxy, C1-5 alkylsulfonylamino, arylsulfonylamino, C1-5alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atommay be independently mono or di-substituted by C1-5 alkyl, aryl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl and piperazinyl or heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, quinolinyl and isoquinolinyl, halogen,hydroxy, oxo, carboxy and cyano, R_(f) may be further optionallysubstituted by one or more R_(g);

[0416] R_(g) is selected from the group consisting of C1-5 alkyl, C3-7cycloalkyl, phenyl optionally substituted by one or more groups selectedfrom halogen, methyl or methoxy, naphthyl optionally substituted by oneor more groups selected from halogen, methyl or methoxy, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl; heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl,pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, quinolinyl, isoquinolinyl, quinazolinyland quinoxalinyl, C1-5 alkoxy, aryloxy, arylC1-5alkoxy, C1-5alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoylwherein the nitrogen atom may be independently mono or di-substituted byC1-5 alkyl, aryl, heterocyclyl selected from the group consisting ofpiperidinyl, morpholinyl and piperazinyl or heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, quinolinyl and isoquinolinyl, C1-5alkanoylamino, aroylamino, C1-5 alkylthio wherein the sulfur atom may beoxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom maybe oxidized to a sulfoxide or sulfone, ureido wherein either nitrogenatom may be independently substituted by C1-5 alkyl, aryl, heterocyclylselected from the group consisting of piperidinyl, morpholinyl andpiperazinyl or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, quinolinyland isoquinolinyl, C1-5 alkoxycarbonylamino, aryloxycarbonylamino, C1-5alkylcarbamoyloxy, arylcarbamoyloxy, C1-5 alkylsulfonylamino,arylsulfonylamino, C1-5 alkylaminosulfonyl, arylaminosulfonyl, aminowherein the nitrogen atom may be independently mono or di-substituted byC1-5 alkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl and piperazinyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, quinolinyl andisoquinolinyl, halogen, hydroxy, oxo, carboxy and cyano;

[0417] R_(h) is selected from the group consisting of C1-5 alkyl,phenyl, naphthyl, C1-5 alkoxycarbonyl, aryloxycarbonyl,arylC1-3alkoxycarbonyl, carbamoyl wherein the nitrogen atom may beoptionally mono or di-substituted with a group selected from C1-5 alkyl,C3-6 cycloalkyl, phenyl, naphthyl, arylC1-3alkyl, heterocyclyl selectedfrom the group consisting of pyrrolidinyl, piperidinyl, morpholinyl andpiperazinyl or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, quinolinyland isoquinolinyl, halogen, hydroxy, carboxy and cyano; and

[0418] X is O.

[0419] Yet even more preferred compounds of the formula (II) are thosewherein:

[0420] Y is O;

[0421] R₁ is C1-5 alkyl, C3-6 cycloalkyl, phenyl, naphthyl, heterocyclylselected from the group consisting of piperidinyl, morpholinyl,piperazinyl, pyranyl and thiopyranyl; heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, quinolinyl and isoquinolinyl or amino,wherein R1 is optionally substituted by one or more R_(b);

[0422] R_(b) is selected from the group consisting of C1-3 alkyl, C3-6cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl and piperazinyl,heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, tetrazolyl, pyridinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,quinolinyl and isoquinolinyl, C1-3 alkoxy, phenoxy, C1-3 alkoxycarbonyl,aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom may be independently mono or di-substituted by C1-5 alkyl,phenyl or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, quinolinyland isoquinolinyl, C1-5 alkanoylamino, aroylamino, C1-5 alkylthiowherein the sulfur atom may be oxidized to a sulfoxide or sulfone,arylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, ureido wherein either nitrogen atom may be independentlysubstituted by C1-5alkyl, phenyl or naphthyl; C1-5 alkoxycarbonylamino,C1-5 alkylcarbamoyloxy, arylcarbamoyloxy, C1-5 alkylsulfonylamino,arylsulfonylamino, C1-5 alkylaminosulfonyl, arylaminosulfonyl, aminowherein the nitrogen atom may be independently mono or di-substituted byC1-5alkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of piperidinyl, morpholinyl and piperazinyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, quinolinyl andisoquinolinyl, halogen, hydroxy, oxo, carboxy and cyano, R_(b) may befurther optionally substituted by one or more R_(c);

[0423] R_(c) is selected from the group consisting of C1-3 alkyl, C5-6cycloalkyl, aryl, C1-3 alkoxy, phenoxy, halogen, hydroxy, oxo, carboxyand cyano;

[0424] R₂ is H;

[0425] R₃ is C1-5 alkyl, C3-6 cycloalkyl or phenyl, wherein R₃ isoptionally substituted by one or more R_(d);

[0426] R_(d) is selected from the group consisting of C1-3 alkyl, C3-6cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of piperidinyl, morpholinyl and piperazinyl; heteroarylselected from the group consisting of furanyl, thienyl, thiazolyl,imidazolyl, pyridinyl, indolyl, quinolinyl and isoquinolinyl, C1-5alkoxy, phenoxy, aroyl, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom may beindependently mono or di-substituted by C1-5 alkyl, phenyl, naphthyl,heterocyclyl selected from the group consisting of piperidinyl,morpholinyl and piperazinyl or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl and indolyl, C1-5 alkanoylamino, aroylamino, C1-3alkylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, phenylthio wherein the sulfur atom may be oxidized to asulfoxide or sulfone, ureido wherein either nitrogen atom may beindependently substituted by C1-3 alkyl, phenyl or heteroaryl selectedthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl and indolyl, C1-5 alkoxycarbonylamino, C1-5alkylcarbamoyloxy, arylcarbamoyloxy, C1-5 alkylsulfonylamino,arylsulfonylamino, amino wherein the nitrogen atom may be independentlymono or di-substituted by C1-3 alkyl, phenyl, heterocyclyl selected fromthe group consisting of piperidinyl, morpholinyl and piperazinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl and indolyl,halogen, hydroxy, oxo, carboxy and cyano, R_(d) may be furtheroptionally substituted by one or more R_(d);

[0427] R_(e) is selected from the group consisting of C1-5 alkyl, C5-6cycloalkyl, phenyl, naphthyl, arylC1-3alkyl, C1-5 alkoxy, phenoxy,arylC1-3alkoxy, aroyl, amino, halogen, hydroxy, oxo, carboxy and cyano;

[0428] R₄ is H;

[0429] R₆ is H, C1-5 alkyl, C3-6 cycloalkyl, phenyl or cyano, wherein R₆is optionally substituted by one or more R_(f);

[0430] R_(f) is selected from the group consisting of C1-3 alkyl, C3-6cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl and piperazinyl;heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, quinolinyland isoquinolinyl, C1-5 alkoxy, aryloxy, arylC1-3alkoxy,heteroarylC1-3alkoxy, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom may beindependently mono or di-substituted by C1-5 alkyl, phenyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyridinyl and indolyl, C1-5alkanoylamino, aroylamino, C1-3 alkylthio wherein the sulfur atom may beoxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom maybe oxidized to a sulfoxide or sulfone, arylC1-3alkylthio wherein thesulfur atom may be oxidized to a sulfoxide or sulfone, ureido whereineither nitrogen atom may be independently substituted by C1-5 alkyl orphenyl, C1-5 alkoxycarbonylamino, C1-5 alkylsulfonylamino,arylsulfonylamino, amino wherein the nitrogen atom may be independentlymono or di-substituted by C1-5 alkyl, phenyl, naphthyl, heterocyclylselected from the group consisting of piperidinyl, morpholinyl andpiperazinyl or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl,halogen, hydroxy, oxo, carboxy and cyano, R_(f) may be furtheroptionally substituted by one or more R_(g);

[0431] R_(g) is selected from the group consisting of C1-3 alkyl, C5-6cycloalkyl, phenyl optionally substituted by one or more groups selectedfrom halogen or methyl, heterocyclyl selected from the group consistingof pyrrolidinyl, piperidinyl, morpholinyl and piperazinyl, heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyridinyl, pyrimidinyl, pyrazinyl andindolyl, C1-5 alkoxy, aryloxy, arylC1-3alkoxy, C1-5 alkoxycarbonyl,aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom may be independently mono or di-substituted by C1-5 alkylor aryl, C1-5 alkanoylamino, aroylamino, C1-5 alkylthio wherein thesulfur atom may be oxidized to a sulfoxide or sulfone, arylthio whereinthe sulfur atom may be oxidized to a sulfoxide or sulfone, ureidowherein either nitrogen atom may be independently substituted by C1-5alkyl or aryl, C1-5 alkoxycarbonylamino, aryloxycarbonylamino, C1-5alkylcarbamoyloxy, arylcarbamoyloxy, C1-5 alkylsulfonylamino,arylsulfonylamino, C1-5 alkylaminosulfonyl, arylaminosulfonyl, aminowherein the nitrogen atom may be independently mono or di-substituted byC1-5 alkyl or aryl, halogen, hydroxy, oxo, carboxy and cyano;

[0432] R_(h) is selected from the group consisting of C1-5 alkyl,phenyl, C1-5 alkoxycarbonyl, aryloxycarbonyl, arylC1-3alkoxycarbonyl,carbamoyl wherein the nitrogen atom may be optionally mono ordi-substituted with C1-5 alkyl, C3-6 cycloalkyl, phenyl, naphthyl orarylC1-3alkyl; halogen, hydroxy, carboxy and cyano.

[0433] Still yet even more preferred compounds of the formula(II) arethose wherein:

[0434] R₁ is C1-3 alkyl, C5-6 cycloalkyl, phenyl, naphthyl, heterocyclylselected from the group consisting of piperidinyl, morpholinyl,piperazinyl, pyranyl and thiopyranyl; heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl and indolyl or amino, wherein R₁ is optionallysubstituted by one or more R_(b);

[0435] R_(b) is selected from the group consisting of C1-3 alkyl, C5-6cycloalkyl, phenyl, heterocyclyl selected from the group consisting ofpiperidinyl, morpholinyl and piperazinyl; heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, imidazolyl, tetrazolyl,pyridinyl, indolyl, benzofuranyl, benzothienyl, benzimidazolyl,benzthiazolyl, quinolinyl and isoquinolinyl, C1-3 alkoxy, C1-3alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoylwherein the nitrogen atom may be independently mono or di-substituted byC1-3 alkyl, phenyl or heteroaryl selected from the group consisting ofpyrrolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl and benzthiazolyl C1-5 alkanoylamino, aroylamino, C1-3alkylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, arylthio wherein the sulfur atom may be oxidized to a sulfoxideor sulfone, ureido wherein either nitrogen atom may be independentlysubstituted by C1-3alkyl or phenyl, C1-5 alkylsulfonylamino,arylsulfonylamino, amino wherein the nitrogen atom may be independentlymono or di-substituted by C1-3alkyl, phenyl, heterocyclyl selected fromthe group consisting of piperidinyl, morpholinyl and piperazinyl orheteroaryl selected from the group consisting of pyrrolyl, imidazolyl,pyridinyl, indolyl, benzofuranyl, benzothienyl, benzimidazolyl,benzthiazolyl, quinolinyl and isoquinolinyl, halogen, hydroxy, oxo,carboxy and cyano, R_(b) may be further optionally substituted by one ormore R_(c);

[0436] R_(c) is selected from the group consisting of C1-3 alkyl, C5-6cycloalkyl, C1-3 alkoxy, halogen and hydroxy;

[0437] R₃ is C1-5 alkyl, C5-6 cycloalkyl or phenyl wherein R₃ isoptionally substituted by one or more R_(d);

[0438] R_(d) is selected from the group consisting of C1-3 alkyl, C3-6cycloalkyl, phenyl, naphthyl, 4-piperidinyl, 4-morpholinyl, piperazinyl,furanyl, thienyl, thiazolyl, imidazolyl, pyridinyl, indolyl, C1-5alkoxy, phenoxy, aroyl, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom may beindependently mono or di-substituted by C1-5 alkyl or phenyl, C1-5alkanoylamino, C1-3 alkylthio wherein the sulfur atom may be oxidized toa sulfoxide or sulfone, ureido wherein either nitrogen atom may beindependently substituted by C1-3 alkyl or phenyl, C1-5alkoxycarbonylamino, C1-5 alkylsulfonylamino, arylsulfonylamino, aminowherein the nitrogen atom may be independently mono or di-substituted byC1-3 alkyl or phenyl, halogen, hydroxy, oxo, carboxy and cyano, R_(d)may be further optionally substituted by one or more R_(e);

[0439] R_(e) is selected from the group consisting of C1-5 alkyl, C5-6cycloalkyl, phenyl, benzyl, C1-5 alkoxy, phenoxy, benzyloxy, aroyl,halogen, hydroxy, oxo, carboxy and cyano;

[0440] R₅ is H or C1-3alkyl;

[0441] R₆ is H, C1-5 alkyl, phenyl or cyano, wherein R₆ is optionallysubstituted by one or more R_(f);

[0442] R_(f) is selected from the group consisting of C1-3 alkyl, C3-6cycloalkyl, phenyl, naphthyl, furanyl, thienyl, thiazolyl, imidazolyl,pyridinyl, indolyl, C1-3 alkoxy, benzyloxy, pyridylC1-3alkoxy,thienylC1-3alkoxy, furanylC1-3alkoxy, C1-3 alkoxycarbonyl,phenoxyoxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom may be independently mono or di-substituted by C1-3 alkylor phenyl, C1-5 alkanoylamino, aroylamino, methylthio wherein the sulfuratom may be oxidized to a sulfoxide or sulfone, benzylthio wherein thesulfur atom may be oxidized to a sulfoxide or sulfone, ureido whereineither nitrogen atom may be independently substituted by C1-5 alkyl orphenyl, C1-3 alkoxycarbonylamino, amino wherein the nitrogen atom may beindependently mono or di-substituted by C1-5 alkyl or phenyl, halogen,hydroxy, oxo, carboxy and cyano, R_(f) may be further optionallysubstituted by one or more R_(g);

[0443] R_(g) is selected from the group consisting of C1-3 alkyl, phenyloptionally substituted by one or more groups selected from the groupconsisting of halogen and methyl, heterocyclyl selected from the groupconsisting of piperidinyl, morpholinyl and piperazinyl; heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl andpyridinyl, C1-3 alkoxy, aryloxy, benzyloxy, C1-5 alkoxycarbonyl, C1-5alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom may beindependently mono or di-substituted by C1-5 alkyl or phenyl, C1-5alkanoylamino, aroylamino, C1-5 alkylthio wherein the sulfur atom may beoxidized to a sulfoxide or sulfone, ureido wherein either nitrogen atommay be independently substituted by C1-5 alkyl or phenyl, C1-5alkoxycarbonylamino, C1-5 alkylcarbamoyloxy, arylcarbamoyloxy, C1-3alkylsulfonylamino, arylsulfonylamino, C1-3 alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom may be independentlymono or di-substituted by C1-3 alkyl or phenyl, halogen, hydroxy, oxo,carboxy and cyano;

[0444] R_(h) is selected from the group consisting of C1-3 alkyl,phenyl, C1-3 alkoxycarbonyl, phenoxyoxycarbonyl, benzyloxy, carbamoylwherein the nitrogen atom may be optionally mono or di-substituted witha group selected from the group consisting of C1-5 alkyl, phenyl andbenzyl, halogen, hydroxy, carboxy and cyano.

[0445] Even more preferred compounds of the formula (II) are thosewherein:

[0446] R₁ is C5-6 cycloalkyl, phenyl, naphthyl, piperidinyl,morpholinyl, piperazinyl, pyranyl, thiopyranyl, furanyl, thienyl,pyrrolyl or amino, wherein R₁ is optionally substituted by one or moreR_(b);

[0447] R_(b) is selected from the group consisting of C1-3 alkyl, C5-6cycloalkyl, phenyl, furanyl, thienyl, pyrrolyl, imidazolyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, C1-3 alkoxy,C1-3 alkoxycarbonyl, carbamoyl wherein the nitrogen atom may beindependently mono or di-substituted by C1-3 alkyl or phenyl; C1-5alkanoylamino, aroylamino, ureido wherein either nitrogen atom may beindependently substituted by C1-3 alkyl or phenyl;, C1-5alkylsulfonylamino, arylsulfonylamino, amino wherein the nitrogen atommay be independently mono or di-substituted by C1-3alkyl or phenyl,halogen, hydroxy, oxo, carboxy and cyano, R_(b) may be furtheroptionally substituted by one or more R_(c);

[0448] R_(c) is selected from the group consisting of C1-3alkyl,C1-3alkoxy, halogen and hydroxy;

[0449] R₃ is C1-5 alkyl, C5-6 cycloalkyl or phenyl, wherein R₃ isoptionally substituted by one or more groups of the formula R_(d);

[0450] R_(d) is selected from the group consisting of C1-3 alkyl, C3-6cycloalkyl, phenyl, naphthyl, 4-piperidinyl, furanyl, thienyl,thiazolyl, imidazolyl, pyridinyl, indolyl, C1-3 alkoxy, C1-5alkoxycarbonyl, C1-5 alkanoyloxy, benzoyloxy, carbamoyl wherein thenitrogen atom may be independently mono or di-substituted by C1-3 alkylor phenyl, C1-5 alkanoylamino, C1-3 alkylthio wherein the sulfur atommay be oxidized to a sulfoxide or sulfone, C1-3 alkoxycarbonylamino,C1-3 alkylsulfonylamino, amino wherein the nitrogen atom may beindependently mono or di-substituted by C1-3 alkyl or phenyl, halogen,hydroxy, oxo, carboxy and cyano, R_(d) may be further optionallysubstituted by one or more R_(e);

[0451] R_(e) is selected from the group consisting of C1-3 alkyl,phenyl, benzyl, C1-3 alkoxy, phenoxy, benzyloxy, benzoyl, halogen,hydroxy, oxo, carboxy and cyano;

[0452] wherein the configuration at the stereocenter defined by R₂ andR₃ and the carbon they are attached to is defined as L;

[0453] R₅ is H or methyl;

[0454] R₆ is C1-5 alkyl, phenyl or cyano wherein R₆ is optionallysubstituted by one or more groups of the formula R_(f);

[0455] R_(f) is selected from the group consisting of methyl, C3-6cycloalkyl, phenyl, naphthyl, furanyl, thienyl, thiazolyl, imidazolyl,pyridinyl, indolyl, C1-3 alkoxy, benzyloxy, pyridylC1-3alkoxy,thienylC1-3alkoxy, furanylC1-3alkoxy, C1-5 alkanoylamino, aroylamino,methylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, benzylthio wherein the sulfur atom may be oxidized to asulfoxide or sulfone, C1-3 alkoxycarbonylamino, amino wherein thenitrogen atom may be independently mono or di-substituted by C1-5 alkylor phenyl, halogen, hydroxy, oxo, carboxy and cyano, R_(f) may befurther optionally substituted by one or more R_(g);

[0456] R_(g) is selected from the group consisting of C1-3 alkyl, phenyloptionally substituted by one or more groups selected from halogen ormethyl, C1-3 alkoxy, aryloxy, benzyloxy, C1-3 alkoxycarbonyl, carbamoylwherein the nitrogen atom may be independently mono or di-substituted byC1-3 alkyl or phenyl, C1-5 alkanoylamino, aroylamino, amino wherein thenitrogen atom may be independently mono or di-substituted by C1-3 alkylor phenyl, halogen, hydroxy, oxo, carboxy and cyano;

[0457] R_(b) is selected from the group consisting of C1-3 alkyl,phenyl, C1-3 alkoxycarbonyl, benzyloxy and carboxy.

[0458] Much more preferred compounds of formula (II) are those wherein:

[0459] R₁ is cyclohexyl, phenyl, naphthyl, piperidinyl, morpholinyl,piperazinyl, pyranyl, thiopyranyl or amino wherein R₁ is optionallysubstituted by one or more R_(b);

[0460] R_(b) is selected from the group consisting of C1-3 alkyl, C5-6cycloalkyl, phenyl, furanyl, thienyl, pyrrolyl, imidazolyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, C1-3 alkoxy,C1-3 alkoxycarbonyl, carbamoyl wherein the nitrogen atom may beindependently mono or di-substituted by C1-3 alkyl or phenyl, C1-5alkanoylamino, aroylamino, C1-5 alkylsulfonylamino, arylsulfonylamino,amino wherein the nitrogen atom may be independently mono ordi-substituted by C1-3 alkyl, halogen, hydroxy, oxo, carboxy and cyano,R_(b) may be further optionally substituted by one or more R_(c);

[0461] R_(c) is selected from the group consisting of C1-3 alkoxy,halogen and hydroxy,

[0462] R₃ is C1-5 alkyl or C5-6 cycloalkyl wherein R₃ is optionallysubstituted by one or more R_(d);

[0463] R_(d) is selected from the group consisting of methyl, C3-6cycloalkyl, phenyl, naphthyl, thienyl, imidazolyl, pyridinyl, indolyl,C1-4 alkoxy, C1-5 alkanoylamino, methylthio wherein the sulfur atom maybe oxidized to a sulfoxide or sulfone, halogen, hydroxy, oxo, carboxyand cyano, R_(d) may be further optionally substituted by one or moreR_(e);

[0464] R_(e) is selected from the group consisting of methyl, phenyl,benzyl, methoxy, phenoxy, benzyloxy, benzoyl, halogen and hydroxy;

[0465] R₆ is C1-5 alkyl or phenyl, wherein R₆ is optionally substitutedby one or more R_(f);

[0466] R_(f) is selected from the group consisting of C3-6 cycloalkyl,phenyl, naphthyl, thienyl, imidazolyl, pyridinyl, indolyl, methoxy,benzyloxy, C1-3 alkanoylamino, methylthio wherein the sulfur atom may beoxidized to a sulfoxide or sulfone, benzylthio wherein the sulfur atommay be oxidized to a sulfoxide or sulfone, methoxycarbonylamino, aminowherein the nitrogen atom may be independently mono or di-substituted byC1-3 alkyl, halogen, hydroxy, carboxy and cyano, R_(f) may be furtheroptionally substituted by one or more R_(g);

[0467] R_(g) is selected from the group consisting of methyl, phenyloptionally substituted by one or more groups selected from halogen ormethyl, methoxy, phenoxy, benzyloxy, methoxycarbonyl, amino wherein thenitrogen atom may be independently mono or di-substituted by C1-3 alkylor phenyl, halogen, hydroxy and carboxy;

[0468] R_(h) is selected from the group consisting of vinyl, phenyl,methoxycarbonyl, benzyloxycarbonyl and carboxy;

[0469] Penultimately preferred compounds of the formula (II) are thosewherein:

[0470] R₁ is cyclohexyl, phenyl, naphthyl, piperidinyl, morpholinyl,piperazinyl, pyranyl or thiopyranyl, wherein R₁ is optionallysubstituted by one or more R_(b);

[0471] R_(b) is selected from the group consisting of pyrrolyl,imidazolyl, indolyl, benzimidazolyl, methoxy, methoxycarbonyl, aminowherein the nitrogen atom may be independently mono or di-substituted byC1-3 alkyl, halogen, hydroxy and carboxy, R_(b) may be furtheroptionally substituted by one or more R_(c);

[0472] R_(c) is selected from the group consisting of methoxy, halogenand hydroxy;

[0473] R_(d) is selected from the group consisting of methyl, C3-6cycloalkyl, phenyl, naphthyl, C1-4 alkoxy, C1-3 alkanoylamino,methylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, halogen, hydroxy, oxo, carboxy and cyano, R_(d) may be furtheroptionally substituted by one or more R_(e);

[0474] R_(e) is selected from the group consisting of methyl, phenyl,methoxy, halogen and hydroxy;

[0475] R₅ is H;

[0476] R_(f) is selected from the group consisting of C5-6 cycloalkyl,phenyl, naphthyl, thienyl, indolyl, methoxy, benzyloxy, methylthiowherein the sulfur atom may be oxidized to a sulfoxide or sulfone,benzylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, methoxycarbonylamino, halogen, hydroxy, carboxy and cyano,R_(f) may be further optionally substituted by one or more R_(g);

[0477] R_(g) is selected from the group consisting of methyl, phenyloptionally substituted by halogen, methoxy, phenoxy, benzyloxy,methoxycarbonyl, halogen, hydroxy and carboxy;

[0478] R_(h) is vinyl or phenyl.

[0479] Ultimately preferred compounds of formula (II) are those wherein:

[0480] R₁ is phenyl, naphthyl or 4-morpholinyl wherein R₁ is optionallysubstituted by one or more R_(b);

[0481] R_(b) is selected from the group consisting of benzimidazolyl,methoxy and dimethylamino R_(b) may be further optionally substituted byR_(c) wherein R_(c) is a halogen atom;

[0482] R₃ is C1-5 alkyl wherein R₃ is optionally substituted by one ormore R_(d);

[0483] R_(d) is selected from the group consisting of C3-6 cycloalkyl,phenyl or naphthyl, R_(d) may be further optionally substituted by oneor more R_(e);

[0484] R_(e) is selected from the group consisting of methyl andhalogen,

[0485] R_(f) is selected from the group consisting of C5-6 cycloalkyl,phenyl, naphthyl, indolyl, benzyloxy, methylthio wherein the sulfur atommay be oxidized to a sulfoxide or sulfone, benzylthio wherein the sulfuratom may be oxidized to a sulfoxide or sulfone, halogen and carboxy,R_(f) may be further optionally substituted by one or more R_(g);

[0486] R_(g) is selected from the group consisting of methyl, methoxy,methoxycarbonyl, halogen and hydroxy.

[0487] In another embodiment of the invention, there are providedcompounds of the formula (Ia):

[0488] wherein:

[0489] A is —C(Y)— or —SO₂—

[0490] Y is O, S or NR, wherein R_(a) is selected from the groupconsisting of H, alkyl, aryl, alkoxy, aryloxy, alkylamino and arylamino;

[0491] R₁ is alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl or aminowherein R₁ is optionally substituted by one or more R_(b);

[0492] R_(b) is selected from the group consisting of alkyl, cycloalkyl,aryl, heterocyclyl, heteroaryl, alkoxy, aryloxy, alkanoyl, aroyl,alkoxycarbonyl, aryloxycarbonyl, alkanoyloxy, aroyloxy, carbamoylwherein the nitrogen atom may be independently mono or di-substituted byalkyl, aryl, heterocyclyl or heteroaryl, alkanoylamino, aroylamino,alkylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, arylthio wherein the sulfur atom may be oxidized to a sulfoxideor sulfone, ureido wherein either nitrogen atom may be independentlysubstituted by alkyl, aryl, heterocyclyl or heteroaryl,alkoxycarbonylamino, aryloxycarbonylamino, alkylcarbamoyloxy,arylcarbamoyloxy, alkylsulfonylamino, arylsulfonylamino,alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atommay be independently mono or di-substituted by alkyl, aryl, heterocyclylor heteroaryl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino andguanidino; R_(b) may be further optionally substituted by one or moreR_(c);

[0493] R_(c) is selected from the group consisting of alkyl, cycloalkyl,aryl, heterocyclyl, heteroaryl, arylalkyl, alkoxy, aryloxy, arylalkoxy,alkanoyl, aroyl, amino wherein the nitrogen atom may be independentlymono or di-substituted by alkyl, aryl, heterocyclyl or heteroaryl,halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino;

[0494] R₂ is H or alkyl;

[0495] R₃ is H, C2-8alkyl, cycloalkyl, aryl, heterocyclyl or heteroaryl,wherein R₃ is optionally substituted by one or more R_(d);

[0496] R_(d) is selected from the group consisting of alkyl, cycloalkyl,aryl, heterocyclyl, heteroaryl, alkoxy, aryloxy, arylalkoxy,alkoxycarbonyl, aryloxycarbonyl, alkanoyl, aroyl, alkanoyloxy, aroyloxy,carbamoyl wherein the nitrogen atom may be independently mono ordi-substituted by alkyl, aryl, heterocyclyl or heteroaryl,alkanoylamino, aroylamino, alkylthio wherein the sulfur atom may beoxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom maybe oxidized to a sulfoxide or sulfone, ureido wherein either nitrogenatom may be independently substituted by alkyl, aryl, heterocyclyl orheteroaryl, alkoxycarbonylamino, aryloxycarbonylamino,alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino,arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino whereinthe nitrogen atom may be independently mono or di-substituted by alkyl,aryl, heterocyclyl or heteroaryl, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino, R_(d) may be further optionallysubstituted by one or more R_(e);

[0497] R_(e) is selected from the group consisting of alkyl, cycloalkyl,aryl, arylalkyl, alkoxy, aryloxy, arylalkoxy, alkanoyl, aroyl, amino,halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino;

[0498] R₄ is H or alkyl;

[0499] R₅ is H or alkyl;

[0500] R₆ is H, alkyl, cycloalkyl, aryl, heterocyclyl, aryl, heteroarylor cyano, wherein R₆ is optionally substituted by one or more R_(f);

[0501] R_(f) is selected from the group consisting of alkyl, cycloalkyl,aryl, heterocyclyl, heteroaryl, alkoxy, aryloxy, arylalkoxy, alkanoyl,aroyl, alkoxycarbonyl, aryloxycarbonyl, alkanoyloxy, aroyloxy,heteroarylalkoxy, carbamoyl wherein the nitrogen atom may beindependently mono or di-substituted by alkyl, aryl, heterocyclyl orheteroaryl, alkanoylamino, aroylamino, alkylcarbamoyl, arylcarbamoyl,alkylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, arylthio wherein the sulfur atom may be oxidized to a sulfoxideor sulfone, arylalkylthio wherein the sulfur atom may be oxidized to asulfoxide or sulfone, ureido wherein either nitrogen atom may beindependently substituted by alkyl, aryl, heterocyclyl or heteroaryl,alkoxycarbonylamino, aryloxycarbonylamino, alkylcarbamoyloxy,arylcarbamoyloxy, alkylsulfonylamino, arylsulfonylamino,alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atommay be independently mono or di-substituted by alkyl, aryl, heterocyclylor heteroaryl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino andguanidino, R_(f) may be further optionally substituted by one or moreR_(g);

[0502] R_(g) is selected from the group consisting of alkyl, cycloalkyl,aryl optionally substituted by one or more groups selected from halogen,methyl or methoxy, heterocyclyl, heteroaryl, alkoxy, aryloxy,arylalkoxy, alkoxycarbonyl, aryloxycarbonyl, alkanoyloxy, aroyloxy,carbamoyl wherein the nitrogen atom may be independently mono ordi-substituted by alkyl, aryl, heterocyclyl or heteroaryl,alkanoylamino, aroylamino, alkylcarbamoyl, arylcarbamoyl, alkylthiowherein the sulfur atom may be oxidized to a sulfoxide or sulfone,arylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, ureido wherein either nitrogen atom may be independentlysubstituted by alkyl, aryl, heterocyclyl or heteroaryl,alkoxycarbonylamino, aryloxycarbonylamino, alkylcarbamoyloxy,arylcarbamoyloxy, alkylsulfonylamino, arylsulfonylamino,alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atommay be independently mono or di-substituted by alkyl, aryl, heterocyclylor heteroaryl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino andguanidino;

[0503] or R₅ and R₆ together with the carbon they are attached form acarbocyclic ring of 3 to 6 carbon atoms, the carbocyclic ring beingoptionally substituted with one or more R_(h);

[0504] R_(h) is selected from the group consisting of alkyl, aryl,alkoxycarbonyl, aryloxycarbonyl, arylalkoxycarbonyl, carbamoyl whereinthe nitrogen atom may be optionally mono or di-substituted with a groupselected from alkyl, cycloalkyl, aryl, arylalkyl, heterocyclyl,heteroaryl, halogen, hydroxy, carboxy and cyano;

[0505] X is O, S or N—OH;

[0506] and the pharmaceutically acceptable salts, esters or tautomersthereof;

[0507] with the following provisos:

[0508] when Y is O and R₆ is arylalkyl or heteroarylalkyl then R₁ cannotbe alkyl, cycloalkyl, aryl, heteroaryl, cycloalkyl-alkyl, aryl-alkyl oraryl-cycloalkyl;

[0509] when R₅ is H then R₆ cannot be H; and

[0510] when R₁ is C1 alkyl then R_(b) cannot be carbamoyl,alkanoylamino, aroylamino, ureido, alkoxycarbonylamino,aryloxycarbonylamino, alkylsulfonylamino, arylsulfonylamino, amino,amidino or guanidino wherein each said R_(b) is linked to said R₁ viathe nitrogen atom thereof.

[0511] Preferred compounds of the formula (IIa) are those wherein:

[0512] Y is O, S or NR_(a) wherein R_(a) is H, alkyl or aryl;

[0513] R₁ is C1-8alkyl, C3-7cycloalkyl, aryl, heterocyclyl selected fromthe group consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl, indolinyl, pyranyl and thiopyranyl,heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl, phenoxazinyl, and amino wherein R1 is optionallysubstituted by one or more R_(b);

[0514] R_(b) is selected from the group consisting of C1-8 alkyl, C3-7cycloalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl, heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl,isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl,thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl,isoindolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl or phenoxazinyl, C1-8 alkoxy, aryloxy, C1-8alkoxycarbonyl, aryloxycarbonyl, C1-8 alkanoyloxy, aroyloxy, carbamoylwherein the nitrogen atom may be independently mono or di-substituted byC1-8 alkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl, or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl,isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl,thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl,isoindolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, C1-8 alkanoylamino,aroylamino, C1-8 alkylthio wherein the sulfur atom may be oxidized to asulfoxide or sulfone, arylthio wherein the sulfur atom may be oxidizedto a sulfoxide or sulfone, ureido wherein either nitrogen atom may beindependently substituted by alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl, or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, purinyl, quinolinyl, isoquinolinyl,quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyl or phenoxazinyl,alkoxycarbonylamino, aryloxycarbonylamino, alkylcarbamoyloxy,arylcarbamoyloxy, alkylsulfonylamino, arylsulfonylamino,alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atommay be independently mono or di-substituted by alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, pyrazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl and phenoxazinyl, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino, guanidino; R_(b) may be further optionally substitutedby one or more R_(c);

[0515] R_(c) is selected from the group consisting of C1-8 alkyl, C3-6cycloalkyl, aryl, C1-8 alkoxy, aryloxy, halogen, hydroxy, oxo, carboxy,cyano, nitro, amidino and guanidino;

[0516] R₃ is H, C2-8 alkyl, C3-7 cycloalkyl, aryl wherein R₃ isoptionally substituted by one or more R_(d);

[0517] R_(d) is selected from the group consisting of C1-8 alkyl, C3-7cycloalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl,isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl,thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl,isoindolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, C1-8 alkoxy, aryloxy,alkanoyl, aroyl, C1-8 alkoxycarbonyl, aryloxycarbonyl, C1-8 alkanoyloxy,aroyloxy, carbamoyl wherein the nitrogen atom may be independently monoor di-substituted by C1-8 alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl, or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, purinyl, quinolinyl, isoquinolinyl,quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyl and phenoxazinyl,C1-8 alkanoylamino, aroylamino, C1-8 alkylthio wherein the sulfur atommay be oxidized to a sulfoxide or sulfone, arylthio wherein the sulfuratom may be oxidized to a sulfoxide or sulfone, ureido wherein eithernitrogen atom may be independently substituted by alkyl, aryl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl and phenoxazinyl, alkoxycarbonylamino,aryloxycarbonylamino, alkylcarbamoyloxy, arylcarbamoyloxy,alkylsulfonylamino, arylsulfonylamino, alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom may be independentlymono or di-substituted by alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, purinyl, quinolinyl, isoquinolinyl,quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyl and phenoxazinyl,halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino, guanidino, R_(d)may be further optionally substituted by one or more R_(e);

[0518] R_(e) is selected from the group consisting of C1-8 alkyl, C3-6cycloalkyl, aryl, arylalkyl, C1-8 alkoxy, aryloxy, arylalkoxy, aroyl,amino, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino andguanidino;

[0519] R₆ is H, C1-8 alkyl, C3-7 cycloalkyl, aryl or cyano, wherein R₆is optionally substituted by one or more R_(f);

[0520] R_(f) is selected from the group consisting of C1-8 alkyl, C3-7cycloalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl,isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl,thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl,isoindolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, C1-8 alkoxy, aryloxy,arylC1-8alkoxy, heteroarylC1-8alkoxy, C1-8 alkoxycarbonyl,aryloxycarbonyl, C1-8 alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom may be independently mono or di-substituted by C1-8 alkyl,aryl, heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl and phenoxazinyl, C1-8 alkanoylamino, aroylamino, C1-8alkylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, arylthio wherein the sulfur atom may be oxidized to a sulfoxideor sulfone, arylC1-8 alkylthio wherein the sulfur atom may be oxidizedto a sulfoxide or sulfone, ureido wherein either nitrogen atom may beindependently substituted by alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl, or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, purinyl, quinolinyl, isoquinolinyl,quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyl and phenoxazinyl,alkoxycarbonylamino, aryloxycarbonylamino, alkylcarbamoyloxy,arylcarbamoyloxy, alkylsulfonylamino, arylsulfonylamino,alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atommay be independently mono or di-substituted by alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl,oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyridinyl,pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidinoand guanidino, R_(f) may be further optionally substituted by one ormore R_(g);

[0521] R_(g) is selected from the group consisting of C1-8 alkyl, C3-7cycloalkyl, aryl optionally substituted by one or more groups selectedfrom halogen, methyl or methoxy, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl; heteroaryl selected from the group consistingof furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl,pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl,thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl,isoindolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, C1-8 alkoxy, aryloxy,arylC1-8alkoxy, C1-8 alkoxycarbonyl, aryloxycarbonyl, C1-8 alkanoyloxy,aroyloxy, carbamoyl wherein the nitrogen atom may be independently monoor di-substituted by C1-8 alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl, or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, purinyl, quinolinyl, isoquinolinyl,quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyl and phenoxazinyl,C1-8 alkanoylamino, aroylamino, C1-8 alkylthio wherein the sulfur atommay be oxidized to a sulfoxide or sulfone, arylthio wherein the sulfuratom may be oxidized to a sulfoxide or sulfone, ureido wherein eithernitrogen atom may be independently substituted by alkyl, aryl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl and phenoxazinyl, alkoxycarbonylamino,aryloxycarbonylamino, alkylcarbamoyloxy, arylcarbamoyloxy,alkylsulfonylamino, arylsulfonylamino, alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom may be independentlymono or di-substituted by alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl, or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, purinyl, quinolinyl, isoquinolinyl,quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyl and phenoxazinyl,halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino, and guanidino;

[0522] or R₅ and R₆ together with the carbon they are attached form acarbocyclic ring of 3 to 6 carbon atoms, the carbocyclic ring beingoptionally substituted with one or more R_(h);

[0523] R_(h) is selected from the group consisting of C1-8 alkyl, aryl,C1-8 alkoxycarbonyl, aryloxycarbonyl, arylC1-8alkoxycarbonyl, carbamoylwherein the nitrogen atom may be optionally mono or di-substituted witha group selected from C1-8 alkyl, C3-7 cycloalkyl, aryl, arylC1-8alkyl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl and phenoxazinyl, halogen, hydroxy, carboxy, and cyano;and

[0524] X is O or S.

[0525] More preferred compounds of the formula (IIa) are those wherein:

[0526] Y is O or S;

[0527] R₁ is C1-5 alkyl, C3-7 cycloalkyl, phenyl, naphthyl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl, indolinyl, pyranyl andthiopyranyl, heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl,tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl or amino; wherein R1 is optionallysubstituted by one or more R_(b);

[0528] R_(b) is selected from the group consisting of C1-5 alkyl, C3-7cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl;, heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,quinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl, C1-5 alkoxy,aryloxy, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy,aroyloxy, carbamoyl wherein the nitrogen atom may be independently monoor di-substituted by C1-8 alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl, or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,quinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl, C1-5alkanoylamino, aroylamino, C1-5 alkylthio wherein the sulfur atom may beoxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom maybe oxidized to a sulfoxide or sulfone, ureido wherein either nitrogenatom may be independently substituted by alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl,pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, quinolinyl, isoquinolinyl, quinazolinyland quinoxalinyl, C1-5 alkoxycarbonylamino, aryloxycarbonylamino, C1-5alkylcarbamoyloxy, arylcarbamoyloxy, C1-5 alkylsulfonylamino,arylsulfonylamino, C1-5 alkylaminosulfonyl, arylaminosulfonyl, aminowherein the nitrogen atom may be independently mono or di-substituted byalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl, or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl,tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino, R_(b) may be further optionallysubstituted by one or more R_(c);

[0529] R_(c) is selected from the group consisting of C1-5 alkyl, C3-6cycloalkyl, aryl, C1-5 alkoxy, aryloxy, halogen, hydroxy, oxo, carboxy,cyano, nitro, amidino and guanidino;

[0530] R₂ is H or C1-3 alkyl;

[0531] R₃ is H, C2-5 alkyl, C3-7 cycloalkyl, aryl wherein R₃ isoptionally substituted by one or more R_(d);

[0532] R_(d) is selected from the group consisting of C1-5 alkyl, C3-7cycloalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl,tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, C1-5 alkoxy, aryloxy, C1-5alkanoyl,aroyl, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy,carbamoyl wherein the nitrogen atom may be independently mono ordi-substituted by C1-5 alkyl, aryl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl, or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,quinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl, C1-5alkanoylamino, aroylamino, C1-5 alkylthio wherein the sulfur atom may beoxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom maybe oxidized to a sulfoxide or sulfone, ureido wherein either nitrogenatom may be independently substituted by C1-5 alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, or heteroarylselected the group consisting of furanyl, thienyl, pyrrolyl, oxazolyl,thiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl,pyrazinyl, indolyl, benzofuranyl, benzothienyl, benzimidazolyl,benzthiazolyl, quinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl,C1-5 alkoxycarbonylamino, aryloxycarbonylamino, C1-5 alkylcarbamoyloxy,arylcarbamoyloxy, C1-5 alkylsulfonylamino, arylsulfonylamino, C1-5alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atommay be independently mono or di-substituted by C1-5 alkyl, aryl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl,pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, quinolinyl, isoquinolinyl, quinazolinyland quinoxalinyl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidinoand guanidino, R_(d) may be further optionally substituted by one ormore R_(e);

[0533] R_(e) is selected from the group consisting of C1-5 alkyl, C3-6cycloalkyl, aryl, arylalkyl, C1-5 alkoxy, aryloxy, arylC1-5alkoxy,aroyl, amino, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino andguanidino;

[0534] R₄ is H or C1-3 alkyl

[0535] R₅ is H or C1-8 alkyl

[0536] R₆ is H, C1-5 alkyl, C3-7 cycloalkyl, aryl or cyano, wherein R₆is optionally substituted by one or more R_(f);

[0537] R_(f) is selected from the group consisting of C1-5 alkyl, C3-7cycloalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl,tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, C1-5 alkoxy, aryloxy, arylC1-5alkoxy,heteroarylC1-5alkoxy, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom may beindependently mono or di-substituted by C1-5 alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl,pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, quinolinyl, isoquinolinyl, quinazolinyland quinoxalinyl, C1-5 alkanoylamino, aroylamino, C1-5 alkylthio whereinthe sulfur atom may be oxidized to a sulfoxide or sulfone, arylthiowherein the sulfur atom may be oxidized to a sulfoxide or sulfone,arylC1-5 alkylthio wherein the sulfur atom may be oxidized to asulfoxide or sulfone, ureido wherein either nitrogen atom may beindependently substituted by C1-5 alkyl, aryl, heterocyclyl selectedfrom the group consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,quinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl, C1-5alkoxycarbonylamino, aryloxycarbonylamino, C1-5 alkylcarbamoyloxy,arylcarbamoyloxy, C1-5 alkylsulfonylamino, arylsulfonylamino, C1-5alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atommay be independently mono or di-substituted by C1-5 alkyl, aryl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl,pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, quinolinyl, isoquinolinyl, quinazolinyland quinoxalinyl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidinoand guanidino, R_(f) may be further optionally substituted by one ormore R_(g);

[0538] R_(g) is selected from the group consisting of C1-5 alkyl, C3-7cycloalkyl, aryl optionally substituted by one or more groups selectedfrom halogen, methyl or methoxy, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl, heteroaryl selected from the group consistingof furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl,triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, quinolinyl,isoquinolinyl, quinazolinyl and quinoxalinyl, C1-5 alkoxy, aryloxy,arylC1-5alkoxy, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy,aroyloxy, carbamoyl wherein the nitrogen atom may be independently monoor di-substituted by C1-5 alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,quinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl, C1-5alkanoylamino, aroylamino, C1-5 alkylthio wherein the sulfur atom may beoxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom maybe oxidized to a sulfoxide or sulfone, ureido wherein either nitrogenatom may be independently substituted by C1-5 alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl,pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, quinolinyl, isoquinolinyl, quinazolinyland quinoxalinyl, C1-5 alkoxycarbonylamino, aryloxycarbonylamino, C1-5alkylcarbamoyloxy, arylcarbamoyloxy, C1-5 alkylsulfonylamino,arylsulfonylamino, C1-5 alkylaminosulfonyl, arylaminosulfonyl, aminowherein the nitrogen atom may be independently mono or di-substituted byC1-5 alkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl, or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl,tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino;

[0539] or R₅ and R₆ together with the carbon they are attached form acarbocyclic ring of 3 to 6 carbon atoms, the carbocyclic ring beingoptionally substituted with one or more R_(h);

[0540] R_(h) is selected from the group consisting of C1-5 alkyl, aryl,C1-5 alkoxycarbonyl, aryloxycarbonyl, arylC1-5alkoxycarbonyl, carbamoylwherein the nitrogen atom may be optionally mono or di-substituted witha group selected from C1-5 alkyl, C3-7 cycloalkyl, aryl, arylC1-5alkyl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl,pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, quinolinyl, isoquinolinyl, quinazolinyland quinoxalinyl, halogen, hydroxy, carboxy and cyano.

[0541] Even more preferred compounds of the formula (IIa) are thosewherein:

[0542] Y is O;

[0543] R₁ is C1-5 alkyl, C3-7 cycloalkyl, phenyl, naphthyl, heterocyclylselected from the group consisting of piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl, pyranyl and thiopyranyl; heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, quinolinyl andisoquinolinyl; or amino wherein R₁ is optionally substituted by one ormore R_(b);

[0544] R_(b) is selected from the group consisting of C1-5 alkyl, C3-7cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl; heteroaryl selected from the group consistingof furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl,tetrazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, quinolinyl and isoquinolinyl, C1-5alkoxy, aryloxy, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy,aroyloxy, carbamoyl wherein the nitrogen atom may be independently monoor di-substituted by C1-5 alkyl, phenyl, naphthyl, heterocyclyl selectedfrom the group consisting of pyrrolidinyl, piperidinyl, morpholinyl,piperazinyl and indolinyl, or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, tetrazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, quinolinyl and isoquinolinyl, C1-5alkanoylamino, aroylamino, C1-5 alkylthio wherein the sulfur atom may beoxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom maybe oxidized to a sulfoxide or sulfone, ureido wherein either nitrogenatom may be independently substituted by alkyl or aryl, C1-5alkoxycarbonylamino, aryloxycarbonylamino, C1-5 alkylcarbamoyloxy,arylcarbamoyloxy, C1-5 alkylsulfonylamino, arylsulfonylamino, C1-5alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atommay be independently mono or di-substituted by alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, quinolinyl andisoquinolinyl, halogen, hydroxy, oxo, carboxy, cyano and nitro, R_(b)may be further optionally substituted by one or more R_(c);

[0545] R_(c) is selected from the group consisting of C1-5 alkyl, C3-6cycloalkyl, aryl, C1-5 alkoxy, aryloxy, halogen, hydroxy, oxo, carboxyand cyano;

[0546] R₂ is H or methyl;

[0547] R₃ is H, C2-5 alkyl, C3-7 cycloalkyl or phenyl wherein R₃ isoptionally substituted by one or more R_(d);

[0548] R_(d) is selected from the group consisting of C1-3 alkyl, C3-6cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of piperidinyl, morpholinyl and piperazinyl, heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, quinolinyl andisoquinolinyl, C1-5 alkoxy, aryloxy, aroyl, C1-5 alkoxycarbonyl,aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom may be independently mono or di-substituted by C1-5 alkyl,aryl, heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl and piperazinyl or heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, quinolinyl and isoquinolinyl, C1-5alkanoylamino, aroylamino, C1-5 alkylthio wherein the sulfur atom may beoxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom maybe oxidized to a sulfoxide or sulfone, ureido wherein either nitrogenatom may be independently substituted by C1-5 alkyl, phenyl, naphthyl,heterocyclyl selected from the group consisting of piperidinyl,morpholinyl and piperazinyl or heteroaryl selected the group consistingof furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl,pyridinyl, indolyl, benzofuranyl, benzothienyl, benzimidazolyl,benzthiazolyl, quinolinyl and isoquinolinyl, C1-5 alkoxycarbonylamino,aryloxycarbonylamino, C1-5 alkylcarbamoyloxy, arylcarbamoyloxy, C1-5alkylsulfonylamino, arylsulfonylamino, C1-5 alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom may be independentlymono or di-substituted by C1-5 alkyl, phenyl, naphthyl, heterocyclylselected from the group consisting of piperidinyl, morpholinyl andpiperazinyl or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, quinolinyland isoquinolinyl, halogen, hydroxy, oxo, carboxy and cyano, R_(d) maybe further optionally substituted by one or more R_(e);.

[0549] R_(e) is selected from the group consisting of C1-5 alkyl, C3-6cycloalkyl, aryl, arylC1-5alkyl, C1-5 alkoxy, aryloxy, arylC1-3alkoxy,aroyl, amino, halogen, hydroxy, oxo, carboxy and cyano;

[0550] R₄ is H or methyl;

[0551] R₅ is H or C1-5 alkyl;

[0552] R₆ is H, C1-5 alkyl, C3-7 cycloalkyl, phenyl, naphthyl or cyano,wherein R₆ is optionally substituted by one or more R_(f);.

[0553] R_(f) is selected from the group consisting of C1-5 alkyl, C3-7cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl; heteroaryl selected from the group consistingof furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl,triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, quinolinyl,isoquinolinyl, quinazolinyl and quinoxalinyl, C1-5 alkoxy, aryloxy,arylC1-5alkoxy, heteroarylC1-5alkoxy, C1-5 alkoxycarbonyl,aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom may be independently mono or di-substituted by C1-5 alkyl,aryl, heterocyclyl selected from the group consisting of piperidinyl,morpholinyl and piperazinyl or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, quinolinyl and isoquinolinyl, C1-5alkanoylamino, aroylamino, C1-5 alkylthio wherein the sulfur atom may beoxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom maybe oxidized to a sulfoxide or sulfone, arylC1-5 alkylthio wherein thesulfur atom may be oxidized to a sulfoxide or sulfone, ureido whereineither nitrogen atom may be independently substituted by C1-5 alkyl,aryl, heterocyclyl selected from the group consisting of piperidinyl,morpholinyl and piperazinyl or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, quinolinyl and isoquinolinyl, C1-5alkoxycarbonylamino, aryloxycarbonylamino, C1-5 alkylcarbamoyloxy,arylcarbamoyloxy, C1-5 alkylsulfonylamino, arylsulfonylamino, C1-5alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atommay be independently mono or di-substituted by C1-5 alkyl, aryl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl and piperazinyl or heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, quinolinyl and isoquinolinyl, halogen,hydroxy, oxo, carboxy and cyano, R_(f) may be further optionallysubstituted by one or more R_(g);

[0554] R_(g) is selected from the group consisting of C1-5 alkyl, C3-7cycloalkyl, phenyl optionally substituted by one or more groups selectedfrom halogen, methyl or methoxy, naphthyl optionally substituted by oneor more groups selected from halogen, methyl or methoxy, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl; heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl,pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, quinolinyl, isoquinolinyl, quinazolinyland quinoxalinyl, C1-5 alkoxy, aryloxy, arylC1-5alkoxy, C1-5alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoylwherein the nitrogen atom may be independently mono or di-substituted byC1-5 alkyl, aryl, heterocyclyl selected from the group consisting ofpiperidinyl, morpholinyl and piperazinyl or heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, quinolinyl and isoquinolinyl, C1-5alkanoylamino, aroylamino, C1-5 alkylthio wherein the sulfur atom may beoxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom maybe oxidized to a sulfoxide or sulfone, ureido wherein either nitrogenatom may be independently substituted by C1-5 alkyl, aryl, heterocyclylselected from the group consisting of piperidinyl, morpholinyl andpiperazinyl or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, quinolinyland isoquinolinyl, C1-5 alkoxycarbonylamino, aryloxycarbonylamino, C1-5alkylcarbamoyloxy, arylcarbamoyloxy, C1-5 alkylsulfonylamino,arylsulfonylamino, C1-5 alkylaminosulfonyl, arylaminosulfonyl, aminowherein the nitrogen atom may be independently mono or di-substituted byC1-5 alkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl and piperazinyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, quinolinyl andisoquinolinyl, halogen, hydroxy, oxo, carboxy and cyano;

[0555] or R₅ and R₆ together with the carbon they are attached form acarbocyclic ring of 3 to 6 carbon atoms, the carbocyclic ring beingoptionally substituted with one or more R_(h);

[0556] R_(h) is selected from the group consisting of C1-5 alkyl,phenyl, naphthyl, C1-5 alkoxycarbonyl, aryloxycarbonyl,arylC1-3alkoxycarbonyl, carbamoyl wherein the nitrogen atom may beoptionally mono or di-substituted with a group selected from C1-5 alkyl,C3-6 cycloalkyl, phenyl, naphthyl, arylC1-3alkyl, heterocyclyl selectedfrom the group consisting of pyrrolidinyl, piperidinyl, morpholinyl andpiperazinyl or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, quinolinyland isoquinolinyl, halogen, hydroxy, carboxy and cyano; and

[0557] X is O.

[0558] Yet even more preferred compounds of the formula (IIa) are thosewherein:

[0559] Y is O;

[0560] R₁ is C1-5 alkyl, C3-6 cycloalkyl, phenyl, naphthyl, heterocyclylselected from the group consisting of piperidinyl, morpholinyl,piperazinyl, pyranyl and thiopyranyl; heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, quinolinyl and isoquinolinyl or amino,wherein R1 is optionally substituted by one or more R_(b);

[0561] R_(b) is selected from the group consisting of C1-3 alkyl, C3-6cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl and piperazinyl,heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, tetrazolyl, pyridinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,quinolinyl and isoquinolinyl, C1-3 alkoxy, phenoxy, C1-3 alkoxycarbonyl,aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom may be independently mono or di-substituted by C1-5 alkyl,phenyl or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, quinolinyland isoquinolinyl, C1-5 alkanoylamino, aroylamino, C1-5 alkylthiowherein the sulfur atom may be oxidized to a sulfoxide or sulfone,arylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, ureido wherein either nitrogen atom may be independentlysubstituted by C1-5alkyl, phenyl or naphthyl; C1-5 alkoxycarbonylamino,C1-5 alkylcarbamoyloxy, arylcarbamoyloxy, C1-5 alkylsulfonylamino,arylsulfonylamino, C1-5 alkylaminosulfonyl, arylaminosulfonyl, aminowherein the nitrogen atom may be independently mono or di-substituted byC1-5alkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of piperidinyl, morpholinyl and piperazinyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, quinolinyl andisoquinolinyl, halogen, hydroxy, oxo, carboxy and cyano, R_(b) may befurther optionally substituted by one or more R_(c);

[0562] R_(c) is selected from the group consisting of C1-3 alkyl, C5-6cycloalkyl, aryl, C1-3 alkoxy, phenoxy, halogen, hydroxy, oxo, carboxyand cyano;

[0563] R₂ is H;

[0564] R₃ is C2-5 alkyl, C3-6 cycloalkyl or phenyl, wherein R₃ isoptionally substituted by one or more R_(d);

[0565] R_(d) is selected from the group consisting of C1-3 alkyl, C3-6cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of piperidinyl, morpholinyl and piperazinyl; heteroarylselected from the group consisting of furanyl, thienyl, thiazolyl,imidazolyl, pyridinyl, indolyl, quinolinyl and isoquinolinyl, C1-5alkoxy, phenoxy, aroyl, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom may beindependently mono or di-substituted by C1-5 alkyl, phenyl, naphthyl,heterocyclyl selected from the group consisting of piperidinyl,morpholinyl and piperazinyl or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl and indolyl, C1-5 alkanoylamino, aroylamino, C1-3alkylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, phenylthio wherein the sulfur atom may be oxidized to asulfoxide or sulfone, ureido wherein either nitrogen atom may beindependently substituted by C1-3 alkyl, phenyl or heteroaryl selectedthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl and indolyl, C1-5 alkoxycarbonylamino, C1-5alkylcarbamoyloxy, arylcarbamoyloxy, C1-5 alkylsulfonylamino,arylsulfonylamino, amino wherein the nitrogen atom may be independentlymono or di-substituted by C1-3 alkyl, phenyl, heterocyclyl selected fromthe group consisting of piperidinyl, morpholinyl and piperazinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl and indolyl,halogen, hydroxy, oxo, carboxy and cyano, R_(d) may be furtheroptionally substituted by one or more R_(c);

[0566] R_(e) is selected from the group consisting of C1-5 alkyl, C5-6cycloalkyl, phenyl, naphthyl, arylC1-3alkyl, C1-5 alkoxy, phenoxy,arylC1-3alkoxy, aroyl, amino, halogen, hydroxy, oxo, carboxy and cyano;

[0567] R₄ is H;

[0568] R₆ is H, C1-5 alkyl, C3-6 cycloalkyl, phenyl or cyano, wherein R₆is optionally substituted by one or more R_(f);

[0569] R_(f) is selected from the group consisting of C1-3 alkyl, C3-6cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl and piperazinyl;heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, quinolinyland isoquinolinyl, C1-5 alkoxy, aryloxy, arylC1-3alkoxy,heteroarylC1-3alkoxy, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom may beindependently mono or di-substituted by C1-5 alkyl, phenyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyridinyl and indolyl, C1-5alkanoylamino, aroylamino, C1-3 alkylthio wherein the sulfur atom may beoxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom maybe oxidized to a sulfoxide or sulfone, arylC1-3alkylthio wherein thesulfur atom may be oxidized to a sulfoxide or sulfone, ureido whereineither nitrogen atom may be independently substituted by C1-5 alkyl orphenyl, C1-5 alkoxycarbonylamino, C1-5 alkylsulfonylamino,arylsulfonylamino, amino wherein the nitrogen atom may be independentlymono or di-substituted by C1-5 alkyl, phenyl, naphthyl, heterocyclylselected from the group consisting of piperidinyl, morpholinyl andpiperazinyl or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl,halogen, hydroxy, oxo, carboxy and cyano, R_(f) may be furtheroptionally substituted by one or more R_(g);

[0570] R_(g) is selected from the group consisting of C1-3 alkyl, C5-6cycloalkyl, phenyl optionally substituted by one or more groups selectedfrom halogen or methyl, heterocyclyl selected from the group consistingof pyrrolidinyl, piperidinyl, morpholinyl and piperazinyl, heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyridinyl, pyrimidinyl, pyrazinyl andindolyl, C1-5 alkoxy, aryloxy, arylC1-3alkoxy, C1-5 alkoxycarbonyl,aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom may be independently mono or di-substituted by C1-5 alkylor aryl, C1-5 alkanoylamino, aroylamino, C1-5 alkylthio wherein thesulfur atom may be oxidized to a sulfoxide or sulfone, arylthio whereinthe sulfur atom may be oxidized to a sulfoxide or sulfone, ureidowherein either nitrogen atom may be independently substituted by C1-5alkyl or aryl, C1-5 alkoxycarbonylamino, aryloxycarbonylamino, C1-5alkylcarbamoyloxy, arylcarbamoyloxy, C1-5 alkylsulfonylamino,arylsulfonylamino, C1-5 alkylaminosulfonyl, arylaminosulfonyl, aminowherein the nitrogen atom may be independently mono or di-substituted byC1-5 alkyl or aryl, halogen, hydroxy, oxo, carboxy and cyano;

[0571] or R₅ and R₆ together with the carbon they are attached form acarbocyclic ring of 3 to 6 carbon atoms, the carbocyclic ring beingoptionally substituted with one or more R_(h);

[0572] R_(h) is selected from the group consisting of C1-5 alkyl,phenyl, C1-5 alkoxycarbonyl, aryloxycarbonyl, arylC1-3alkoxycarbonyl,carbamoyl wherein the nitrogen atom may be optionally mono ordi-substituted with C1-5 alkyl, C3-6 cycloalkyl, phenyl, naphthyl orarylC1-3alkyl; halogen, hydroxy, carboxy and cyano.

[0573] Still yet even more preferred compounds of the formula(IIa) arethose wherein:

[0574] R₁ is C1-3 alkyl, C5-6 cycloalkyl, phenyl, naphthyl, heterocyclylselected from the group consisting of piperidinyl, morpholinyl,piperazinyl, pyranyl and thiopyranyl; heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl and indolyl or amino, wherein R₁ is optionallysubstituted by one or more R_(b);

[0575] R_(b) is selected from the group consisting of C1-3 alkyl, C5-6cycloalkyl, phenyl, heterocyclyl selected from the group consisting ofpiperidinyl, morpholinyl and piperazinyl; heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, imidazolyl, tetrazolyl,pyridinyl, indolyl, benzofuranyl, benzothienyl, benzimidazolyl,benzthiazolyl, quinolinyl and isoquinolinyl, C1-3 alkoxy, C1-3alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoylwherein the nitrogen atom may be independently mono or di-substituted byC1-3 alkyl, phenyl or heteroaryl selected from the group consisting ofpyrrolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl and benzthiazolyl C1-5 alkanoylamino, aroylamino, C1-3alkylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, arylthio wherein the sulfur atom may be oxidized to a sulfoxideor sulfone, ureido wherein either nitrogen atom may be independentlysubstituted by C1-3alkyl or phenyl, C1-5 alkylsulfonylamino,arylsulfonylamino, amino wherein the nitrogen atom may be independentlymono or di-substituted by C1-3alkyl, phenyl, heterocyclyl selected fromthe group consisting of piperidinyl, morpholinyl and piperazinyl orheteroaryl selected from the group consisting of pyrrolyl, imidazolyl,pyridinyl, indolyl, benzofuranyl, benzothienyl, benzimidazolyl,benzthiazolyl, quinolinyl and isoquinolinyl, halogen, hydroxy, oxo,carboxy and cyano, R_(b) may be further optionally substituted by one ormore R_(c);

[0576] R_(c) is selected from the group consisting of C1-3 alkyl, C5-6cycloalkyl, C1-3 alkoxy, halogen and hydroxy;

[0577] R₃ is C2-5 alkyl, C5-6 cycloalkyl or phenyl wherein R₃ isoptionally substituted by one or more R_(d);

[0578] R_(d) is selected from the group consisting of C1-3 alkyl, C3-6cycloalkyl, phenyl, naphthyl, 4-piperidinyl, 4-morpholinyl, piperazinyl,furanyl, thienyl, thiazolyl, imidazolyl, pyridinyl, indolyl, C1-5alkoxy, phenoxy, aroyl, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom may beindependently mono or di-substituted by C1-5 alkyl or phenyl, C1-5alkanoylamino, C1-3 alkylthio wherein the sulfur atom may be oxidized toa sulfoxide or sulfone, ureido wherein either nitrogen atom may beindependently substituted by C1-3 alkyl or phenyl, C1-5alkoxycarbonylamino, C1-5 alkylsulfonylamino, arylsulfonylamino, aminowherein the nitrogen atom may be independently mono or di-substituted byC1-3 alkyl or phenyl, halogen, hydroxy, oxo, carboxy and cyano, R_(d)may be further optionally substituted by one or more R_(e);

[0579] R_(e) is selected from the group consisting of C1-5 alkyl, C5-6cycloalkyl, phenyl, benzyl, C1-5 alkoxy, phenoxy, benzyloxy, aroyl,halogen, hydroxy, oxo, carboxy and cyano;

[0580] R₅ is H or C1-3alkyl;

[0581] R₆ is H, C1-5 alkyl, phenyl or cyano, wherein R₆ is optionallysubstituted by one or more R_(f);

[0582] R_(f) is selected from the group consisting of C1-3 alkyl, C3-6cycloalkyl, phenyl, naphthyl, furanyl, thienyl, thiazolyl, imidazolyl,pyridinyl, indolyl, C1-3 alkoxy, benzyloxy, pyridylC1-3alkoxy,thienylC1-3alkoxy, furanylC1-3alkoxy, C1-3 alkoxycarbonyl,phenoxyoxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom may be independently mono or di-substituted by C1-3 alkylor phenyl, C1-5 alkanoylamino, aroylamino, methylthio wherein the sulfuratom may be oxidized to a sulfoxide or sulfone, benzylthio wherein thesulfur atom may be oxidized to a sulfoxide or sulfone, ureido whereineither nitrogen atom may be independently substituted by C1-5 alkyl orphenyl, C1-3 alkoxycarbonylamino, amino wherein the nitrogen atom may beindependently mono or di-substituted by C1-5 alkyl or phenyl, halogen,hydroxy, oxo, carboxy and cyano, R_(f) may be further optionallysubstituted by one or more R_(g);

[0583] R_(g) is selected from the group consisting of C1-3 alkyl, phenyloptionally substituted by one or more groups selected from the groupconsisting of halogen and methyl, heterocyclyl selected from the groupconsisting of piperidinyl, morpholinyl and piperazinyl; heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl andpyridinyl, C1-3 alkoxy, aryloxy, benzyloxy, C1-5 alkoxycarbonyl, C1-5alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom may beindependently mono or di-substituted by C1-5 alkyl or phenyl, C1-5alkanoylamino, aroylamino, C1-5 alkylthio wherein the sulfur atom may beoxidized to a sulfoxide or sulfone, ureido wherein either nitrogen atommay be independently substituted by C1-5 alkyl or phenyl, C1-5alkoxycarbonylamino, C1-5 alkylcarbamoyloxy, arylcarbamoyloxy, C1-3alkylsulfonylamino, arylsulfonylamino, C1-3 alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom may be independentlymono or di-substituted by C1-3 alkyl or phenyl, halogen, hydroxy, oxo,carboxy and cyano;

[0584] or R₅ and R₆ together with the carbon they are attached form acarbocyclic ring of 3 to 5 carbon atoms, the carbocyclic ring beingoptionally substituted with one or more R_(h);

[0585] R_(h) is selected from the group consisting of C1-3 alkyl,phenyl, C1-3 alkoxycarbonyl, phenoxyoxycarbonyl, benzyloxy, carbamoylwherein the nitrogen atom may be optionally mono or di-substituted witha group selected from the group consisting of C1-5 alkyl, phenyl andbenzyl, halogen, hydroxy, carboxy and cyano.

[0586] Even more preferred compounds of the formula (II) are thosewherein:

[0587] R₁ is C5-6 cycloalkyl, phenyl, naphthyl, piperidinyl,morpholinyl, piperazinyl, pyranyl, thiopyranyl, furanyl, thienyl,pyrrolyl or amino, wherein R₁ is optionally substituted by one or moreR_(b);

[0588] R_(b) is selected from the group consisting of C1-3 alkyl, C5-6cycloalkyl, phenyl, furanyl, thienyl, pyrrolyl, imidazolyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, C1-3 alkoxy,C1-3 alkoxycarbonyl, carbamoyl wherein the nitrogen atom may beindependently mono or di-substituted by C1-3 alkyl or phenyl; C1-5alkanoylamino, aroylamino, ureido wherein either nitrogen atom may beindependently substituted by C1-3alkyl or phenyl;, C1-5alkylsulfonylamino, arylsulfonylamino, amino wherein the nitrogen atommay be independently mono or di-substituted by C1-3alkyl or phenyl,halogen, hydroxy, oxo, carboxy and cyano, R_(b) may be furtheroptionally substituted by one or more R_(c);

[0589] R_(c) is selected from the group consisting of C1-3alkyl,C1-3alkoxy, halogen and hydroxy;

[0590] R₃ is C2-5 alkyl, C5-6 cycloalkyl or phenyl, wherein R₃ isoptionally substituted by one or more groups of the formula R_(d);

[0591] R_(d) is selected from the group consisting of C1-3 alkyl, C3-6cycloalkyl, phenyl, naphthyl, 4-piperidinyl, furanyl, thienyl,thiazolyl, imidazolyl, pyridinyl, indolyl, C1-3 alkoxy, C1-5alkoxycarbonyl, C1-5 alkanoyloxy, benzoyloxy, carbamoyl wherein thenitrogen atom may be independently mono or di-substituted by C1-3 alkylor phenyl, C1-5 alkanoylamino, C1-3 alkylthio wherein the sulfur atommay be oxidized to a sulfoxide or sulfone, C1-3 alkoxycarbonylamino,C1-3 alkylsulfonylamino, amino wherein the nitrogen atom may beindependently mono or di-substituted by C1-3 alkyl or phenyl, halogen,hydroxy, oxo, carboxy and cyano, R_(d) may be further optionallysubstituted by one or more R_(e);

[0592] R_(e) is selected from the group consisting of C1-3 alkyl,phenyl, benzyl, C1-3 alkoxy, phenoxy, benzyloxy, benzoyl, halogen,hydroxy, oxo, carboxy and cyano;

[0593] wherein the configuration at the stereocenter defined by R₂ andR₃ and the carbon they are attached to is defined as L;

[0594] R₅ is H or methyl;

[0595] R₆ is C1-5 alkyl, phenyl or cyano wherein R₆ is optionallysubstituted by one or more groups of the formula R_(f);

[0596] R_(f) is selected from the group consisting of methyl, C3-6cycloalkyl, phenyl, naphthyl, furanyl, thienyl, thiazolyl, imidazolyl,pyridinyl, indolyl, C1-3 alkoxy, benzyloxy, pyridylC1-3alkoxy,thienylC1-3alkoxy, furanylC1-3alkoxy, C1-5 alkanoylamino, aroylamino,methylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, benzylthio wherein the sulfur atom may be oxidized to asulfoxide or sulfone, C1-3 alkoxycarbonylamino, amino wherein thenitrogen atom may be independently mono or di-substituted by C1-5 alkylor phenyl, halogen, hydroxy, oxo, carboxy and cyano, R_(f) may befurther optionally substituted by one or more R_(g);

[0597] R_(g) is selected from the group consisting of C1-3 alkyl, phenyloptionally substituted by one or more groups selected from halogen ormethyl, C1-3 alkoxy, aryloxy, benzyloxy, C1-3 alkoxycarbonyl, carbamoylwherein the nitrogen atom may be independently mono or di-substituted byC1-3 alkyl or phenyl, C1-5 alkanoylamino, aroylamino, amino wherein thenitrogen atom may be independently mono or di-substituted by C1-3 alkylor phenyl, halogen, hydroxy, oxo, carboxy and cyano;

[0598] or R₅ and R₆ together with the carbon they are attached form acarbocyclic ring of 3 to 5 carbon atoms, the carbocyclic ring beingoptionally substituted with one or more R_(h);

[0599] R_(h) is selected from the group consisting of C1-3 alkyl,phenyl, C1-3 alkoxycarbonyl, benzyloxy and carboxy.

[0600] Much more preferred compounds of formula (IIa) are those wherein:

[0601] R₁ is cyclohexyl, phenyl, naphthyl, piperidinyl, morpholinyl,piperazinyl, pyranyl, thiopyranyl or amino wherein R₁ is optionallysubstituted by one or more R_(b);

[0602] R_(b) is selected from the group consisting of C1-3 alkyl, C5-6cycloalkyl, phenyl, furanyl, thienyl, pyrrolyl, imidazolyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, C1-3 alkoxy,C1-3 alkoxycarbonyl, carbamoyl wherein the nitrogen atom may beindependently mono or di-substituted by C1-3 alkyl or phenyl, C1-5alkanoylamino, aroylamino, C1-5 alkylsulfonylamino, arylsulfonylamino,amino wherein the nitrogen atom may be independently mono ordi-substituted by C1-3 alkyl, halogen, hydroxy, oxo, carboxy and cyano,R_(b) may be further optionally substituted by one or more R_(c);

[0603] R_(c) is selected from the group consisting of C1-3 alkoxy,halogen and hydroxy,

[0604] R₃ is C2-5 alkyl or C5-6 cycloalkyl wherein R₃ is optionallysubstituted by one or more R_(d);

[0605] R_(d) is selected from the group consisting of methyl, C3-6cycloalkyl, phenyl, naphthyl, thienyl, imidazolyl, pyridinyl, indolyl,C1-4 alkoxy, C1-5 alkanoylamino, methylthio wherein the sulfur atom maybe oxidized to a sulfoxide or sulfone, halogen, hydroxy, oxo, carboxyand cyano, R_(d) may be further optionally substituted by one or moreR_(e);

[0606] R_(e) is selected from the group consisting of methyl, phenyl,benzyl, methoxy, phenoxy, benzyloxy, benzoyl, halogen and hydroxy;

[0607] R₆ is C1-5 alkyl or phenyl, wherein R₆ is optionally substitutedby one or more R_(f);

[0608] R_(f) is selected from the group consisting of C3-6 cycloalkyl,phenyl, naphthyl, thienyl, imidazolyl, pyridinyl, indolyl, methoxy,benzyloxy, C1-3 alkanoylamino, methylthio wherein the sulfur atom may beoxidized to a sulfoxide or sulfone, benzylthio wherein the sulfur atommay be oxidized to a sulfoxide or sulfone, methoxycarbonylamino, aminowherein the nitrogen atom may be independently mono or di-substituted byC1-3 alkyl, halogen, hydroxy, carboxy and cyano, R_(f) may be furtheroptionally substituted by one or more R_(g);

[0609] R_(g) is selected from the group consisting of methyl, phenyloptionally substituted by one or more groups selected from halogen ormethyl, methoxy, phenoxy, benzyloxy, methoxycarbonyl, amino wherein thenitrogen atom may be independently mono or di-substituted by C1-3 alkylor phenyl, halogen, hydroxy and carboxy;

[0610] or R₅ and R₆ together with the carbon they are attached form acarbocyclic ring of 3 to 5 carbon atoms, the carbocyclic ring beingoptionally substituted with one or more R_(h);

[0611] R_(h) is selected from the group consisting of vinyl, phenyl,methoxycarbonyl, benzyloxycarbonyl and carboxy;

[0612] Penultimately preferred compounds of the formula (IIa) are thosewherein:

[0613] R₁ is cyclohexyl, phenyl, naphthyl, piperidinyl, morpholinyl,piperazinyl, pyranyl or thiopyranyl, wherein R₁ is optionallysubstituted by one or more R_(b);

[0614] R_(b) is selected from the group consisting of pyrrolyl,imidazolyl, indolyl, benzimidazolyl, methoxy, methoxycarbonyl, aminowherein the nitrogen atom may be independently mono or di-substituted byC1-3 alkyl, halogen, hydroxy and carboxy, R_(b) may be furtheroptionally substituted by one or more R_(c);

[0615] R_(c) is selected from the group consisting of methoxy, halogenand hydroxy;

[0616] R_(d) is selected from the group consisting of methyl, C3-6cycloalkyl, phenyl, naphthyl, C1-4 alkoxy, C1-3 alkanoylamino,methylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, halogen, hydroxy, oxo, carboxy and cyano, R_(d) may be furtheroptionally substituted by one or more R_(e);

[0617] R_(e) is selected from the group consisting of methyl, phenyl,methoxy, halogen and hydroxy;

[0618] R₅ is H;

[0619] R_(f) is selected from the group consisting of C5-6 cycloalkyl,phenyl, naphthyl, thienyl, indolyl, methoxy, benzyloxy, methylthiowherein the sulfur atom may be oxidized to a sulfoxide or sulfone,benzylthio wherein the sulfur atom may be oxidized to a sulfoxide orsulfone, methoxycarbonylamino, halogen, hydroxy, carboxy and cyano,R_(f) may be further optionally substituted by one or more R_(g);

[0620] R_(g) is selected from the group consisting of methyl, phenyloptionally substituted by halogen, methoxy, phenoxy, benzyloxy,methoxycarbonyl, halogen, hydroxy and carboxy;

[0621] or R₅ and R₆ together with the carbon they are attached form acarbocyclic ring of 3 carbon atoms, the carbocyclic ring beingoptionally substituted with one or more R_(h);

[0622] R_(h) is vinyl or phenyl.

[0623] Ultimately preferred compounds of formula (IIa) are thosewherein:

[0624] R₁ is phenyl, naphthyl or 4-morpholinyl wherein R₁ is optionallysubstituted by one or more R_(b);

[0625] R_(b) is selected from the group consisting of benzimidazolyl,methoxy and dimethylamino R_(b) may be further optionally substituted byR_(c) wherein R_(c) is a halogen atom;

[0626] R₃ is C2-5 alkyl wherein R₃ is optionally substituted by one ormore R_(d);

[0627] R_(d) is selected from the group consisting of C3-6 cycloalkyl,phenyl or naphthyl, R_(d) may be further optionally substituted by oneor more R_(e);

[0628] R_(e) is selected from the group consisting of methyl andhalogen,

[0629] R_(f) is selected from the group consisting of C5-6 cycloalkyl,phenyl, naphthyl, indolyl, benzyloxy, methylthio wherein the sulfur atommay be oxidized to a sulfoxide or sulfone, benzylthio wherein the sulfuratom may be oxidized to a sulfoxide or sulfone, halogen and carboxy,R_(f) may be further optionally substituted by one or more R_(g);

[0630] R_(g) is selected from the group consisting of methyl, methoxy,methoxycarbonyl, halogen and hydroxy and

[0631] R₅ and R₆ together with the carbon they are attached form acarbocyclic ring of 3 carbon atoms, the carbocyclic ring beingoptionally substituted with one or more R_(h).

[0632] The following are representative compounds according to theinvention:

[0633] N-(4-morpholylinecarbonyl)-L-leucine(1S-cyano-3-phenylpropyl)amide;

[0634]N-(4-morpholinecarbonyl)-L-Homophenylalanine(1S-cyano-3-phenylpropyl)amide;

[0635] N-(5-dimethylaminonaphth-1-ylsulfonyl)-L-leucine(1S-cyano-3-phenylpropyl)amide;

[0636]N-(4-morpholinecarbonyl)-L-leucine-(1S-cyano-3-phenylpropyl)-N-methylamide;

[0637]N-(4-Morpholinecarbonyl)-L-leucine-[1R,S(benzthiazol-2-ylcarbonyl)-3-phenylpropyl]amide;

[0638] N-[(4-Morpholinecarbonyl)-L-leucine-[1R,S-(thiazol-2-ylcarbonyl)-3-phenylpropyl]amide;

[0639] N-(4-Morpholinecarbonyl)-L-leucine-[1R,S-[(1-(3-N-Benzyl)imidazol-2-ylcarbonyl]-3-phenylpropyl]amide;

[0640] N-(4-Morpholinecarbonyl)-L-leucine-[1R,S-(2-imidazolylcarbonyl)-3-phenylpropyl]amide;

[0641] N-(4-morpholinecarbonyl)-L-leucine (cyanomethyl)amide;

[0642] N-(4-Morpholinecarbonyl)-L-leucine [1S-cyano-5-((benzyloxycarbonyl)-amino)-pentyl]amide;

[0643] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-3-phenylpropyl)amide;

[0644] N-(4-Morpholinecarbonyl]-L-leucine-(1S-cyano-5-aminopentyl)amide;

[0645]N-(4-morpholinecarbonyl]-L-phenylalanine-(1S-cyano-3-phenylpropyl)amide;

[0646]N-(4-morpholinecarbonyl)-L-(p-ethoxy)phenylalanine-(1S-cyano-3-phenylpropyl)amide;

[0647] N-(4-Morpholinecarbonyl)-L-leucine-[1S-cyano-4-(benzyloxycarbonylamino)-butyl]amide;

[0648]N-(4-Morpholinecarbonyl)-L-leucine-[1-(benzthiazol-2-ylcarbonyl)-5-[(benzyloxycarbonyl)amino]-pentyl]amide;

[0649] N-(1-naphthylsulfonyl)-L-leucine (1S-cyano-3-phenylpropyl)amide;

[0650] N-(4-morpholinecarbonyl)-L-(4-methyl)leucine(1S-cyano-3-phenylpropyl)amide;

[0651] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-benzyloxyethyl)amide;

[0652] N-(methanesulfonyl)-D-(O-benzyl)serine(1S-cyano-3-phenylpropyl)amide;

[0653] N-(5-dimethylaminonaphth-1-ylsulfonyl)-D-leucine(1R-cyano-3-phenylpropyl)amide;

[0654] N-(4-morpholinecarbonyl)-L-(4-methyl)leucine(1R-cyano-2-benzyloxyethyl)amide;

[0655] N-((4-dimethylaminophenyl)sulfonyl)-L-leucine(1S-cyano-3-(phenylpropyl))amide;

[0656] N-(t-Butoxycarbonyl)-L-leucine[1-(Benzothiazo-2-ylcarbonyl)-3-phenylpropyl]amide;

[0657] N-(5-dimethylaminonaphth-1-ylsulfonyl)-L-leucine[1-(Benzothiazol-2-ylcarbonyl)-3-phenylpropyl]amide;

[0658] N-(4-methoxy-phenylsulfonyl)-L-leucine[1-(Benzothiazol-2-ylcarbonyl)-3-phenylpropyl]amide;

[0659] N-(4-Morpholinecarbonyl)-L-leucine-[1R,S(benzoxazol-2-ylcarbonyl)-3-phenylpropyl]amide;

[0660] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2R-benzyloxypropyl)amide;

[0661] N-(4-Morpholinecarbonyl)-L-leucine-[1R,S-[(4-phenylthiazol-2-yl)-carbonyl]-3-phenylpropyl]amide;

[0662] N-(4-morpholinecarbonyl)-D-leucine(1S-cyano-3-phenylpropyl)amide;

[0663] N-(4-morpholinecarbonyl)-L-leucine[[1-[(6-phenylcarbamoyl)benzothiazol-2-ylcarbonyl]-3-phenylpropyl]]amide;

[0664] N-(methylsulfonyl)-L-leucine[1-(Benzothiazol-2-ylcarbonyl)-3-phenylpropyl]amide;

[0665] N-(4-morpholinecarbonyl)-L-(p-phenyl)phenylalanine(1S-cyano-3-phenylpropyl)amide;

[0666]N-(4-Morpholinecarbonyl)-L-leucine-[1R,S-[(5-phenylthiazol-2-yl)-carbonyl]-3-phenylpropyl]amide;

[0667] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-(benzylsulfanyl)ethyl)amide;

[0668] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-(2-chlorophenyl)methyloxyethyl)amide;

[0669] N-(4-morpholinecarbonyl)-L-phenylglycine(1S-cyano-3-phenylpropyl)amide;

[0670] N-(4-morpholinecarbonyl)-L-leucine[1-(Benzothiazol-2-ylcarbonyl)-2-benzyloxyethyl]amide;

[0671]N-(4-Morpholinecarbonyl]-L-leucine-[[6-(carbomethoxy)-benzoxazol-2-ylcarbonyl]-3-phenylpropyl]amide;

[0672] N-(5-dimethylaminonaphth-1-ylsulfonyl)-L-(4-methyl)leucine(1R-cyano-2-benzyloxyethyl)amide;

[0673] N-(4-morpholinecarbonyl)-L-cyclohexylalanine(1S-cyano-3-phenylpropyl)amide;

[0674]N-(4-Morpholinecarbonyl)-L-leucine-[1R,S-[(4-(4-benzyloxycarbonylamino)phenyl-thiazol-2-yl)-carbonyl]-3-phenylpropyl]amide;

[0675] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-(3-methoxyphenyl)methyloxyethyl)amide;

[0676] N-(4-morpholinecarbonyl)-L-(4-methyl)leucine(1R-cyano-2-(benzylsulfanyl)ethyl)amide;

[0677] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-(benzylsulfonyl)ethyl)amide;

[0678] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-(benzylsulfinyl)ethyl)amide;

[0679] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-((4-methoxyphenyl)methylsulfanyl)ethyl)amide;

[0680] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-((4-methylphenyl)methylsulfanyl)ethyl)amide;

[0681] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-(4-chlorophenyl)methyloxyethyl)amide;

[0682] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-(3-chlorophenyl)methyloxyethyl)amide;

[0683] N-(5-dimethylaminonaphth-1-ylsulfonyl)-L-leucine(1R-cyano-2-benzyloxyethyl)amide;

[0684] N-(4-Morpholinecarbonyl]-L-leucine1S-((2-phenyloxazol-5-yl)carbonyl)-3-phenylpropylamide;

[0685] N-(4-morpholinecarbonyl)-L-(p-phenylcarbonyl)phenylalanine(1S-cyano-3-phenylpropyl)amide;

[0686] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-(2-methylphenyl)methyloxyethyl)amide;

[0687] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-(3-methylphenyl)methyloxyethyl)amide;

[0688] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-(4-methylphenyl)methyloxyethyl)amide;

[0689] N-(4-Morpholinecarbonyl)-L-leucine1RS-((5-phenyloxazol-2-yl)carbonyl)-3-phenylpropylamide;

[0690] N-(4-morpholinecarbonyl)-L-cyclohexylalanine(1R-cyano-2-benzyloxyethyl)amide;

[0691] N-(4-morpholinecarbonyl)-L-nor-leucine(1S-cyano-3-phenylpropyl)amide;

[0692] N-(Benzyloxycarbonyl)-L-(O-t-butyl)serine(1R-cyano-2-benzyloxyethyl)amide;

[0693] N-(4-Morpholinecarbonyl]-L-leucine1S-(oxazol-2-ylcarbonyl)-3-phenylpropylamide;

[0694] N-(4-morpholinecarbonyl)-L-(4-methyl)leucine[1-(Benzothiazol-2-ylcarbonyl)-3-phenylpropyl]amide;

[0695] N-(5-dimethylaminonaphth-1-ylsulfonyl)-L-cyclohexylalanine(1R-cyano-2-benzyloxyethyl)amide;

[0696] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-(3-carbomethoxyphenyl)methyloxyethyl)amide;

[0697] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-(4-carbomethoxyphenyl)methyloxyethyl)amide;

[0698] N-(4-Morpholinecarbonyl]-L-leucine1S-(pyrid-2-ylcarbonyl)-3-phenylpropylamide;

[0699] N-(4-Morpholinecarbonyl)-L-leucine-[1R,S-[(4-(2-benzyloxyamino)phenyl-thiazol-2-yl)-carbonyl]-3-phenylpropyl]amide;

[0700] N-(4-morpholinecarbonyl)-L-(O-t-butyl)serine(1R-cyano-2-benzyloxyethyl)amide;

[0701] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-hydroxyethyl)amide;

[0702] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-3-(carbo-t-butoxy)propyl)amide;

[0703] N-(cyclohexylcarbonyl)-L-leucine(1R-cyano-2-benzyloxyethyl)amide;

[0704] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-3-(carbo-t-butoxy)ethyl)amide;

[0705] N-(4-morpholinecarbonyl)-L-leucine dicyanomethylamide;

[0706] N-(4-morpholinecarbonyl)-L-(2-naphthyl)alanine(1S-cyano-3-phenylpropyl)amide;

[0707] N-(4-morpholinecarbonyl)-L-(O-Benzyl)glutamate(1S-cyano-3-phenylpropyl)amide;

[0708] N-(4-morpholinecarbonyl)-L-homo-tyrosine(1S-cyano-3-phenylpropyl)amide;

[0709] N-(4-morpholinecarbonyl)-L-norvaline(1S-cyano-3-phenylpropyl)amide;

[0710] N-(4-morpholinecarbonyl)-L-(2-chlorophenyl)alanine(1S-cyano-3-phenylpropyl)amide;

[0711] N-Benzoyl-L-leucine (1R-cyano-2-benzyloxyethyl)amide;

[0712]N-(4-morpholinecarbonyl)-L-(4,5-dehydro)leucine(1S-cyano-3-phenylpropyl)amide;

[0713]N-(4-morpholinecarbonyl)-L-(O-methyl)tyrosine(1S-cyano-3-phenylpropyl)amide;

[0714] N-(4-morpholinecarbonyl)-L-iso-leucine(1S-cyano-3-phenylpropyl)amide;

[0715] N-(4-morpholinecarbonyl)-L-(4-nitrophenyl)alanine(1S-cyano-3-phenylpropyl)amide;

[0716] N-(4-morpholinecarbonyl)-L-(4-fluorophenyl)alanine(1S-cyano-3-phenylpropyl)amide;

[0717] N-(4-morpholinecarbonyl)-L-tyrosine(1S-cyano-3-phenylpropyl)amide;

[0718] N-(4-morpholinecarbonyl)-L-(1-naphthyl)alanine(1S-cyano-3-phenylpropyl)amide;

[0719] N-(4-morpholinecarbonyl)-L-methionine(1S-cyano-3-phenylpropyl)amide;

[0720] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-(1-benzyl-4-imidazolyl)ethyl)amide;

[0721] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-(1-benzyl-4-imidazolyl)ethyl)amide;

[0722] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-(carbobenzyloxy)ethyl)amide;

[0723]N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-(carbobenzyloxy)ethyl)amide;

[0724] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-1-phenylmethyl)amide;

[0725] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-1-phenylmethyl)amide;

[0726] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-(4-benzyloxyphenyl)ethyl)amide;

[0727] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-(4-benzyloxyphenyl)ethyl)amide;

[0728] N-(4-morpholinecarbonyl)-L-phenylalanine(1-cyanocyclopropyl)amide;

[0729] N-(4-morpholinecarbonyl)-L-leucine (1-cyanocyclopropyl)amide;

[0730] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-(4-phenylphenyl)ethyl)amide;

[0731] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-(4-phenylphenyl)ethyl)amide;

[0732] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-(4-benzoylphenyl)ethyl)amide;

[0733] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-(4-benzoylphenyl)ethyl) amide;

[0734] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-(1-naphthyl)ethyl)amide;

[0735] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-(1-naphthyl)ethyl)amide;

[0736] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-(2-naphthyl)ethyl)amide;

[0737] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-(2-naphthyl)ethyl)amide;

[0738] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-(2-chlorophenyl)ethyl)amide;

[0739] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-(2-chlorophenyl)ethyl)amide;

[0740] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-(4-chlorophenyl)ethyl)amide;

[0741] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-(4-chlorophenyl)ethyl)amide;

[0742] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-(3,4-dichlorophenyl)ethyl)amide;

[0743] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-(3,4-dichlorophenyl)ethyl)amide;

[0744] N-(4-morpholinecarbonyl)-L-phenylalanine(S-cyanobut-3-ynyl)amide;

[0745] N-(4-morpholinecarbonyl)-L-leucine(1S-cyanobut-3-ynyl)amide;

[0746] N-(4-morpholinecarbonyl)-L-leucine (1S-cyanopropyl)amide;

[0747] N-(4-morpholinecarbonyl)-L-phenylalanine;

[0748] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-(4-(2,6-dichloromethyloxy)phenyl)ethyl)amide;

[0749] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2S-methylbutyl)amide;

[0750] N-(4-morpholinecarbonyl)-L-phenylalanine (1S-cyanopentyl)amide;

[0751] N-(4-morpholinecarbonyl)-L-leucine (1S-cyanopentyl)amide;

[0752] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2,2-dimethylpropyl)amide;

[0753] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2,2-dimethylpropyl)amide;

[0754] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-3-methylbutyl)amide;

[0755] N-(4-morpholinecarbonyl)-L-leucine (1S-cyano-3-methylbutyl)amide;

[0756] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-(4-nitrophenylethyl)amide;

[0757] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-(4-nitrophenylethyl)amide;

[0758] N-(4-morpholinecarbonyl)-L-phenylalanine (1S-cyanobutyl)amide;

[0759] N-(4-morpholinecarbonyl)-L-leucine (1S-cyanobutyl)amide;

[0760] N-(4-morpholinecarbonyl)-L-phenylalanine(1R-cyano-2R-benzyloxypropyl)amide;

[0761] N-(4-morpholinecarbonyl)-L-phenylalanine (1S-cyanoethyl)amide;

[0762] N-(4-morpholinecarbonyl)-L-leucine (1S-cyano ethyl) amide;

[0763] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-3-(carbobenzyloxy)propyl)amide;

[0764] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-3-(carbobenzyloxy)propyl)amide;

[0765] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-(3-benzimidazolyl)ethyl)amide;

[0766] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-(3-benzimidazolyl)ethyl)amide;

[0767] N-(4-morpholinecarbonyl)-L-phenylalanine(1-cyano-1-methylethyl)amide;

[0768] N-(4-morpholinecarbonyl)-L-leucine (1-cyano-1-methylethyl)amide;

[0769] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-(4-hydroxyphenyl)ethyl)amide;

[0770] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-(4-hydroxyphenyl)ethyl)amide;

[0771] N-(4-morpholinecarbonyl)-L-phenylalanine(1S,3-dicyanopropyl)amide;

[0772] N-(4-morpholinecarbonyl)-L-leucine (1S,3-dicyanopropyl)amide;

[0773] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-(4-hydroxy-3-iodophenyl)ethyl)amide;

[0774] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-(4-hydroxy-3-iodophenyl)ethyl)amide;

[0775] N-(4-morpholinecarbonyl)-L-phenylalanine(1S,2-dicyanoethyl)amide;

[0776] N-(4-morpholinecarbonyl)-L-leucine (1S,2-dicyanoethyl)amide;

[0777] N-(4-morpholinecarbonyl)-L-phenylalanine(1R-cyano-2-benzyloxyethyl)amide;

[0778] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-(2-thienyl)ethyl)amide;

[0779] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-(2-thienyl)ethyl)amide;

[0780] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-3-(methylsulfonyl)propyl)amide;

[0781] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-3-(methylsulfonyl)propyl)amide;

[0782] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-phenylethyl)amide;

[0783] N-(4-morpholinecarbonyl)-L-leucine (1S-cyano-2-phenylethyl)amide;

[0784] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-3-(4-hydroxyphenyl)propyl)amide;

[0785] 5 N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-3-(4-hydroxyphenyl)propyl)amide;

[0786] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-cyclohexylethyl)amide;

[0787] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-cyclohexylethyl)amide;

[0788] 10 N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-(3-chlorophenyl) ethyl) amide; and

[0789] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-(3-chlorophenyl)ethyl)amide. 15

[0790] Preferred compounds of the invention include:

[0791] N-(5-dimethylaminonaphth-1-ylsulfonyl)-L-leucine(1S-cyano-3-phenylpropyl)amide;

[0792] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-3-phenylpropyl)amide;

[0793] N-(1-naphthylsulfonyl)-L-leucine (1S-cyano-3-phenylpropyl)amide;

[0794] N-(4-morpholinecarbonyl)-L-(4-methyl)leucine(1S-cyano-3-phenylpropyl)amide;

[0795] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-benzyloxyethyl)amide;

[0796] N-(4-morpholinecarbonyl)-L-(4-methyl)leucine(1R-cyano-2-benzyloxyethyl)amide;

[0797] N-((4-dimethylaminophenyl)sulfonyl)-L-leucine(1S-cyano-3-(phenylpropyl))amide;

[0798] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2R-benzyloxypropyl)amide;

[0799] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-(benzylsulfanyl)ethyl)amide;

[0800] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-(2-chlorophenyl)methyloxyethyl)amide;

[0801] N-(5-dimethylaminonaphth-1-ylsulfonyl)-L-(4-methyl)leucine(1R-cyano-2-benzyloxyethyl)amide;

[0802] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-(3-methoxyphenyl)methyloxyethyl)amide;

[0803] N-(4-morpholinecarbonyl)-L-(4-methyl)leucine(1R-cyano-2-(benzylsulfanyl)ethyl)amide;

[0804] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-(benzylsulfonyl)ethyl)amide;

[0805] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-(benzylsulfinyl)ethyl)amide;

[0806] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-((4-methoxyphenyl)methylsulfanyl)ethyl)amide;

[0807] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-((4-methylphenyl)methylsulfanyl)ethyl)amide;

[0808] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-(4-chlorophenyl)methyloxyethyl)amide;

[0809] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-(3-chlorophenyl)methyloxyethyl)amide;

[0810] N-(5-dimethylaminonaphth-1-ylsulfonyl)-L-leucine(1R-cyano-2-benzyloxyethyl)amide;

[0811] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-(2-methylphenyl)methyloxyethyl)amide;

[0812] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-(3-methylphenyl)methyloxyethyl)amide;

[0813] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-(4-methylphenyl)methyloxyethyl)amide;

[0814] N-(5-dimethylaminonaphth-1-ylsulfonyl)-L-cyclohexylalanine(1R-cyano-2-benzyloxyethyl)amide;

[0815] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-(3-carbomethoxyphenyl)methyloxyethyl)amide;

[0816] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-(4-carbomethoxyphenyl)methyloxyethyl)amide;

[0817] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-hydroxyethyl)amide;

[0818] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-3-(carbo-t-butoxy)propyl)amide;

[0819] N-(cyclohexylcarbonyl)-L-leucine(1R-cyano-2-benzyloxyethyl)amide;

[0820] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-3-(carbo-t-butoxy)ethyl)amide;

[0821] N-(4-morpholylinecarbonyl)-L-leucine(1S-cyano-3-phenylpropyl)amide;

[0822]N-(4-morpholinecarbonyl)-L-Homophenylalanine(1S-cyano-3-phenylpropyl)amide;

[0823] N-(4-morpholinecarbonyl)-L-leucine (cyanomethyl)amide;

[0824] N-(4-Morpholinecarbonyl)-L-leucine [1S-cyano-5-((benzyloxycarbonyl)-amino)-pentyl]amide;

[0825] N-(4-Morpholinecarbonyl]-L-leucine-(1S-cyano-5-aminopentyl)amide;

[0826]N-(4-morpholinecarbonyl]-L-phenylalanine-(1S-cyano-3-phenylpropyl)amide;

[0827]N-(4-morpholinecarbonyl)-L-(p-ethoxy)phenylalanine-(1S-cyano-3-phenylpropyl)amide;

[0828] N-(4-Morpholinecarbonyl)-L-leucine-[1S-cyano-4-(benzyloxycarbonylamino)-butyl]amide;

[0829] N-(4-Morpholinecarbonyl)-L-leucine-[1R,S(benzthiazol-2-ylcarbonyl)-3-phenylpropyl]amide;

[0830]N-(4-Morpholinecarbonyl)-L-leucine-[1R,S(benzoxazol-2-ylcarbonyl)-3-phenylpropyl]amide;

[0831]N-(4-Morpholinecarbonyl)-L-leucine-[1-(benzthiazol-2-ylcarbonyl)-5-[(benzyloxycarbonyl)amino]-pentyl]amide;

[0832]N-(4-Morpholinecarbonyl]-L-leucine-[[6-(carbomethoxy)-benzoxazol-2-ylcarbonyl]-3-phenylpropyl]amide;

[0833] N-(4-morpholinecarbonyl)-L-leucine[[1-[(6-phenylcarbamoyl)benzothiazol-2-ylcarbonyl]-3-phenylpropyl]]amide;

[0834] N-(4-morpholinecarbonyl)-L-(p-phenyl)phenylalanine(1S-cyano-3-phenylpropyl)amide;

[0835] N-(4-morpholinecarbonyl)-L-phenylglycine(1S-cyano-3-phenylpropyl)amide;

[0836] N-(4-morpholinecarbonyl)-L-cyclohexylalanine(1S-cyano-3-phenylpropyl)amide;

[0837] N-(4-Morpholinecarbonyl]-L-leucine1S-((2-phenyloxazol-5-yl)carbonyl)-3-phenylpropylamide;

[0838] N-(4-morpholinecarbonyl)-L-(p-phenylcarbonyl)phenylalanine(1S-cyano-3-phenylpropyl)amide;

[0839] N-(4-Morpholinecarbonyl]-L-leucine1RS-((5-phenyloxazol-2-yl)carbonyl)-3-phenylpropylamide;

[0840] N-(4-Morpholinecarbonyl]-L-leucine1S-(oxazol-2-ylcarbonyl)-3-phenylpropylamide;

[0841] N-(4-morpholinecarbonyl)-L-cyclohexylalanine(1R-cyano-2-benzyloxyethyl)amide;

[0842] N-(4-morpholinecarbonyl)-L-nor-leucine(1S-cyano-3-phenylpropyl)amide;

[0843] N-(4-morpholinecarbonyl)-L-(4-methyl)leucine[1-(Benzothiazol-2-ylcarbonyl)-3-phenylpropyl]amide;

[0844] N-(4-Morpholinecarbonyl]-L-leucine1S-(pyrid-2-ylcarbonyl)-3-phenylpropylamide;

[0845] N-(4-morpholinecarbonyl)-L-(O-t-butyl)serine(1R-cyano-2-benzyloxyethyl)amide;

[0846] N-(4-morpholinecarbonyl)-L-(2-naphthyl)alanine(1S-cyano-3-phenylpropyl)amide;

[0847] N-(4-morpholinecarbonyl)-L-(O-Benzyl)glutamate(1S-cyano-3-phenylpropyl)amide;

[0848] N-(4-morpholinecarbonyl)-L-homo-tyrosine(1S-cyano-3-phenylpropyl)amide;

[0849] N-(4-morpholinecarbonyl)-L-norvaline(1S-cyano-3-phenylpropyl)amide;

[0850] N-(4-morpholinecarbonyl)-L-(2-chlorophenyl)alanine(1S-cyano-3-phenylpropyl)amide;

[0851] N-Benzoyl-L-leucine (1R-cyano-2-benzyloxyethyl)amide;

[0852]N-(4-morpholinecarbonyl)-L-(4,5-dehydro)leucine(1S-cyano-3-phenylpropyl)amide;

[0853]N-(4-morpholinecarbonyl)-L-(O-methyl)tyrosine(1S-cyano-3-phenylpropyl)amide;

[0854] N-(4-morpholinecarbonyl)-L-iso-leucine(1S-cyano-3-phenylpropyl)amide;

[0855] N-(4-morpholinecarbonyl)-L-(4-nitrophenyl)alanine(1S-cyano-3-phenylpropyl)amide;

[0856] N-(4-morpholinecarbonyl)-L-(4-fluorophenyl)alanine(1S-cyano-3-phenylpropyl)amide;

[0857] N-(4-morpholinecarbonyl)-L-tyrosine(1S-cyano-3-phenylpropyl)amide;

[0858] N-(4-morpholinecarbonyl)-L-(1-naphthyl)alanine(1S-cyano-3-phenylpropyl)amide;

[0859] N-(4-morpholinecarbonyl)-L-methionine(1S-cyano-3-phenylpropyl)amide;

[0860] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-(1-benzyl-4-imidazolyl)ethyl)amide;

[0861] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-(1-benzyl-4-imidazolyl)ethyl)amide;

[0862] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-(carbobenzyloxy)ethyl)amide;

[0863]N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-(carbobenzyloxy)ethyl)amide;

[0864] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-1-phenylmethyl)amide;

[0865] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-1-phenylmethyl)amide;

[0866] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-(4-benzyloxyphenyl)ethyl)amide;

[0867] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-(4-benzyloxyphenyl)ethyl)amide;

[0868] N-(4-morpholinecarbonyl)-L-phenylalanine(1-cyanocyclopropyl)amide;

[0869] N-(4-morpholinecarbonyl)-L-leucine (1-cyanocyclopropyl)amide;

[0870] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-(4-phenylphenyl)ethyl)amide;

[0871] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-(4-phenylphenyl)ethyl)amide;

[0872] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-(4-benzoylphenyl)ethyl)amide;

[0873]N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-(4-benzoylphenyl)ethyl)amide;

[0874] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-(1-naphthyl)ethyl)amide;

[0875] N-(4-morpholinecarbonyl)-L-leucine (1S-cyano-2-(1-naphthyl)ethyl) amide;

[0876] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-(2-naphthyl)ethyl)amide;

[0877] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-(2-naphthyl)ethyl)amide;

[0878] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-(2-chlorophenyl) ethyl) amide;

[0879] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-(2-chlorophenyl)ethyl)amide;

[0880] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-(4-chlorophenyl)ethyl)amide;

[0881] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-(4-chlorophenyl)ethyl)amide;

[0882] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-(3,4-dichlorophenyl)ethyl)amide;

[0883] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-(3,4-dichlorophenyl)ethyl)amide;

[0884] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyanobut-3-ynyl)amide;

[0885] N-(4-morpholinecarbonyl)-L-leucine(1S-cyanobut-3-ynyl)amide;

[0886] N-(4-morpholinecarbonyl)-L-leucine (1S-cyanopropyl)amide;

[0887] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-(4-(2,6-dichloromethyloxy)phenyl)ethyl)amide;

[0888] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-(4-(2,6-dichloromethyloxy)phenyl)ethyl)amide;

[0889] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2S-methylbutyl)amide;

[0890] N-(4-morpholinecarbonyl)-L-phenylalanine (1S-cyanopentyl)amide;

[0891] N-(4-morpholinecarbonyl)-L-leucine (1S-cyanopentyl)amide;

[0892] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2,2-dimethylpropyl)amide;

[0893] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2,2-dimethylpropyl)amide;

[0894] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-3-methylbutyl)amide;

[0895] N-(4-morpholinecarbonyl)-L-leucine (1S-cyano-3-methylbutyl)amide;

[0896] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-(4-nitrophenylethyl)amide;

[0897] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-(4-nitrophenylethyl)amide;

[0898] N-(4-morpholinecarbonyl)-L-phenylalanine (1S-cyanobutyl)amide;

[0899] N-(4-morpholinecarbonyl)-L-leucine (1S-cyanobutyl)amide;

[0900] N-(4-morpholinecarbonyl)-L-phenylalanine(1R-cyano-2R-benzyloxypropyl)amide;

[0901] N-(4-morpholinecarbonyl)-L-phenylalanine (1S-cyanoethyl)amide;

[0902] N-(4-morpholinecarbonyl)-L-leucine (1S-cyano ethyl) amide;

[0903] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-3-(carbobenzyloxy)propyl)amide;

[0904] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-3-(carbobenzyloxy)propyl)amide;

[0905] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-(3-benzimidazolyl)ethyl)amide;

[0906] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-(3-benzimidazolyl)ethyl)amide;

[0907] N-(4-morpholinecarbonyl)-L-phenylalanine(1-cyano-1-methylethyl)amide;

[0908] N-(4-morpholinecarbonyl)-L-leucine (1-cyano-1-methylethyl)amide;

[0909] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-(4-hydroxyphenyl)ethyl)amide;

[0910] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-(4-hydroxyphenyl)ethyl)amide;

[0911] N-(4-morpholinecarbonyl)-L-phenylalanine(1S,3-dicyanopropyl)amide;

[0912] N-(4-morpholinecarbonyl)-L-leucine (1S,3-dicyanopropyl)amide;

[0913] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-(4-hydroxy-3-iodophenyl)ethyl)amide;

[0914] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-(4-hydroxy-3-iodophenyl)ethyl)amide;

[0915] N-(4-morpholinecarbonyl)-L-phenylalanine(1S,2-dicyanoethyl)amide;

[0916] N-(4-morpholinecarbonyl)-L-leucine (1S,2-dicyanoethyl)amide;

[0917] N-(4-morpholinecarbonyl)-L-phenylalanine(1R-cyano-2-benzyloxyethyl)amide;

[0918] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-(2-thienyl)ethyl)amide;

[0919] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-(2-thienyl)ethyl)amide;

[0920] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-3-(methylsulfonyl)propyl)amide;

[0921] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-3-(methylsulfonyl)propyl)amide;

[0922] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-phenylethyl)amide;

[0923] N-(4-morpholinecarbonyl)-L-leucine (1S-cyano-2-phenylethyl)amide;

[0924] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-3-(4-hydroxyphenyl)propyl)amide;

[0925] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-3-(4-hydroxyphenyl)propyl)amide;

[0926] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-cyclohexylethyl)amide;

[0927] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-cyclohexylethyl)amide;

[0928] N-(4-morpholinecarbonyl)-L-phenylalanine(1S-cyano-2-(3-chlorophenyl)ethyl)amide; and

[0929] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-(3-chlorophenyl)ethyl)amide.

[0930] More preferred compounds of the invention include:

[0931] N-(4-morpholinecarbonyl)-L-(4-methyl)leucine(1S-cyano-3-phenylpropyl)amide;

[0932] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-benzyloxyethyl)amide;

[0933] N-(4-morpholinecarbonyl)-L-(4-methyl)leucine(1R-cyano-2-benzyloxyethyl)amide;

[0934] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2R-benzyloxypropyl)amide;

[0935] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-(benzylsulfanyl)ethyl)amide;

[0936] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-(2-chlorophenyl)methyloxyethyl)amide;

[0937] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-(4-chlorophenyl)methyloxyethyl)amide;

[0938] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-(3-methoxyphenyl)methyloxyethyl)amide;

[0939] N-(4-morpholinecarbonyl)-L-(4-methyl)leucine(1R-cyano-2-(benzylsulfanyl)ethyl)amide;

[0940] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-(benzylsulfonyl)ethyl)amide;

[0941] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-(benzylsulfinyl)ethyl)amide;

[0942] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-((4-methoxyphenyl)methylsulfanyl)ethyl)amide;

[0943] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-(3-chlorophenyl)methyloxyethyl)amide;

[0944] N-(5-dimethylaminonaphth-1-ylsulfonyl)-L-leucine(1R-cyano-2-benzyloxyethyl)amide;

[0945] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-(2-methylphenyl)methyloxyethyl)amide;

[0946] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-(3-methylphenyl)methyloxyethyl)amide;

[0947] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-(4-methylphenyl)methyloxyethyl)amide;

[0948] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-(3-carbomethoxyphenyl)methyloxyethyl)amide;

[0949] N-(4-morpholinecarbonyl)-L-leucine(1R-cyano-2-(4-carbomethoxyphenyl)methyloxyethyl)amide;

[0950] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-3-(carbo-t-butoxy)propyl)amide;

[0951] N-(4-morpholylinecarbonyl)-L-leucine(1S-cyano-3-phenylpropyl)amide;

[0952]N-(4-Morpholinecarbonyl)-L-leucine-[1S(benzthiazol-2-ylcarbonyl)-3-phenylpropyl]amide;

[0953] N-(4-Morpholinecarbonyl)-L-leucine[1S-cyano-5-((benzyloxycarbonyl)-amino)-pentyl]amide;

[0954]N-(4-Morpholinecarbonyl)-L-leucine-[1R,S(benzoxazol-2-ylcarbonyl)-3-phenylpropyl]amide;

[0955] N-(4-morpholinecarbonyl)-L-leucine[[1-[(6-phenylcarbamoyl)benzothiazol-2-ylcarbonyl]-3-phenylpropyl]]amide;

[0956]N-(4-Morpholinecarbonyl]-L-leucine-[[6-(carbomethoxy)-benzoxazol-2-ylcarbonyl]-3-phenylpropyl]amide;

[0957] N-(4-morpholinecarbonyl)-L-cyclohexylalanine(1S-cyano-3-phenylpropyl)amide;

[0958] N-(4-morpholinecarbonyl)-L-cyclohexylalanine(1R-cyano-2-benzyloxyethyl)amide;

[0959] N-(4-morpholinecarbonyl)-L-nor-leucine(1S-cyano-3-phenylpropyl)amide;

[0960] N-(4-Morpholinecarbonyl]-L-leucine1RS-((5-phenyloxazol-2-yl)carbonyl)-3-phenylpropylamide;

[0961] N-(4-Morpholinecarbonyl]-L-leucine1S-(oxazol-2-ylcarbonyl)-3-phenylpropylamide;

[0962] N-(4-morpholinecarbonyl)-L-(4-methyl)leucine[1-(Benzothiazol-2-ylcarbonyl)-3-phenylpropyl]amide;

[0963] N-(4-morpholinecarbonyl)-L-(2-naphthyl)alanine(1S-cyano-3-phenylpropyl)amide;

[0964] N-(4-morpholinecarbonyl)-L-(2-chlorophenyl)alanine(1S-cyano-3-phenylpropyl)amide;

[0965] N-Benzoyl-L-leucine (1R-cyano-2-benzyloxyethyl)amide;

[0966] N-(4-morpholinecarbonyl)-L-(O-methyl)tyrosine(1S-cyano-3-phenylpropyl)amide;

[0967]N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-(carbobenzyloxy)ethyl)amide;

[0968] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-1-phenylmethyl)amide;

[0969] N-(4-morpholinecarbonyl)-L-leucine (1-cyanocyclopropyl)amide;

[0970] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-(2-chlorophenyl)ethyl)amide;

[0971] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-(4-(2,6-dichloromethyloxy)phenyl)ethyl)amide;

[0972] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-3-(carbobenzyloxy)propyl)amide;

[0973] N-(4-morpholinecarbonyl)-L-leucine (1S,3-dicyanopropyl)amide;

[0974] N-(4-morpholinecarbonyl)-L-leucine (1S,2-dicyanoethyl)amide;

[0975] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-3-(methylsulfonyl)propyl)amide;

[0976] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-3-(4-hydroxyphenyl)propyl)amide; and

[0977] N-(4-morpholinecarbonyl)-L-leucine(1S-cyano-2-cyclohexylethyl)amide.

[0978] Any compounds of this invention containing one or more asymmetriccarbon atoms may occur as racemates and racemic mixtures, singleenantiomers, diastereomeric mixtures and individual diastereomers. Allsuch isomeric forms of these compounds are expressly included in thepresent invention. Each stereogenic carbon may be in the R or Sconfiguration, or a combination of configurations.

[0979] Some of the compounds of formulas (I), (Ia) and formulas (II),(IIa) can exist in more than one tautomeric form. The invention includesall such tautomers.

[0980] It shall be understood by one of ordinary skill in the art thatall compounds of the invention are those which are chemically stable.

[0981] The invention includes pharmaceutically acceptable derivatives ofcompounds of formulas (I), (Ia) and formulas (II), (IIa). A“pharmaceutically acceptable derivative” refers to any pharmaceuticallyacceptable salt or ester of a compound of this invention, or any othercompound which, upon administration to a patient, is capable ofproviding (directly or indirectly) a compound of this invention, apharmacologically active metabolite or pharmacologically active residuethereof. A pharmacologically active metabolite shall be understood tomean any compound of the invention capable of being metabolizedenzymatically or chemically. This includes, for example, hydroxylated oroxidized derivative compounds of the invention.

[0982] In addition, the compounds of this invention include prodrugs ofcompounds of the formulas (I),(Ia) and formulas (II), (IIa). Prodrugsinclude those compounds that, upon simple chemical transformation, aremodified to produce the compounds of the invention. Simple chemicaltransformations include hydrolysis, oxidation and reduction.Specifically, when a prodrug of this invention is administered to apatient, the prodrug may be transformed into a compound of formulas(I),(Ia) or formulas (II), (Ia), thereby imparting the desiredpharmacological effect.

[0983] In order that the invention herein described may be more fullyunderstood, the following detailed description is set forth. As usedherein, the following abbreviations are used:

[0984] BOC or t-BOC is tertiary butoxycarbonyl;

[0985] t-Bu is tertiary butyl;

[0986] DMF is dimethylformamide;

[0987] EtOAc is ethyl acetate;

[0988] THF is tetrahydrofuran;

[0989] Ar is argon;

[0990] TFA is trifluoroacetic acid;

[0991] EDC is 1-(3-dimethylaminopropyl)-3-ethylcarbodimidehydrochloride.

[0992] HOBT is 1-hydroxybenzotriazole

[0993] Also, as used herein, each of the following terms, used alone orin conjunction with other terms, are defined as follows (except wherenoted to the contrary):

[0994] The term “alkyl” refers to a saturated aliphatic radicalcontaining from one to ten carbon atoms or a mono- or polyunsaturatedaliphatic hydrocarbon radical containing from two to twelve carbonatoms, containing at least one double or triple bond, respectively.“Alkyl” refers to both branched and unbranched alkyl groups. Preferredalkyl groups are straight chain alkyl groups containing from one toeight carbon atoms and branched alkyl groups containing from three toeight carbon atoms. More preferred alkyl groups are straight chain alkylgroups containing from one to six carbon atoms and branched alkyl groupscontaining from three to six carbon atoms. It should be understood thatany combination term using an “alk” or “alkyl” prefix refers to analogsaccording to the above definition of “alkyl”. For example, terms such as“alkoxy”, “alkythio” refer to alkyl groups linked to a second group viaan oxygen or sulfur atom. “Alkanoyl refers to an alkyl group linked to acarbonyl group (C═O).

[0995] The term “cycloalkyl” refers to the cyclic analog of an alkylgroup, as defined above. Preferred cycloalkyl groups are saturatedcycloalkyl groups containing from three to eight carbon atoms, and morepreferably three to six carbon atoms.

[0996] The term “aryl” refers to phenyl and naphthyl. “Aroyl” refers toan aryl group linked to a carbonyl group (C═O). The term “halo” refersto a halogen radical selected from fluoro, chloro, bromo or iodo.Preferred halo groups are fluoro, chloro and bromo.

[0997] The term “heteroaryl” refers to a stable 5-8 membered (butpreferably, 5 or 6 membered) monocyclic or 8-11 membered bicyclicaromatic heterocycle radical. Each heterocycle consists of carbon atomsand from 1 to 4 heteroatoms selected from the group consisting ofnitrogen, oxygen and sulfur. As used herein, “nitrogen” and “sulfur”include any oxidized form of nitrogen and sulfur and the quaternizedform of any basic nitrogen. The heterocycle may be attached by any atomof the cycle, which results in the creation of a stable structure.Preferred heteroaryl radicals include, for example, furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolizinyl, indolyl,isoindolyl, benzofuranyl, benzothienyl, indazolyl, benzimidazolyl,benzthiazolyl, benzoxazolyl, purinyl, quinolizinyl, quinolinyl,isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl,naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl,phenothiazinyl or phenoxazinyl,

[0998] The term “heterocycle” refers to a stable 5-8 membered (butpreferably, 5 or 6 membered) monocyclic or 8-11 membered bicyclicheterocycle radical which may be either saturated or unsaturated, and isnon-aromatic. Each heterocycle consists of carbon atoms and from 1 to 4heteroatoms selected from the group consisting of nitrogen, oxygen andsulfur. As used herein, “nitrogen” and “sulfur” include any oxidizedform of nitrogen and sulfur and the quaternized form of any basicnitrogen. The heterocycle may be attached by any atom of the cycle,which results in the creation of a stable structure. Preferredheterocycle radicals include, for example, pyrrolinyl, pyrrolidinyl,pyrazolinyl, pyrazolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,pyranyl, thiopyranyl, piperazinyl and indolinyl.

General Synthetic Methods

[0999] The invention also provides processes of making the present novelcompounds. Compounds of the invention may be prepared by methodsdescribed below. Standard peptide coupling, protection and deprotectionreactions (see for example M. Bodanszky, The Practice of PeptideSynthesis, Springer-Verlag, 1984) are employed in these syntheses.

[1000] Compounds of the invention having formula (II) or (IIa)(nitriles) may be prepared by Method A (Scheme I)

[1001] Scheme I (Method A)

[1002] According to Method A a suitably protected amino acid bearing R₆is allowed to react with ammonia under standard coupling conditions. Anexample of a suitable protecting group is the t-butoxycarbonyl (Boc)group. An example of standard coupling conditions would be combining thestarting materials in the presence of a coupling reagent such as1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC) with1-hydroxybenzotriazole (HOBT), in a suitable solvent such as DMF ormethylene chloride. A base such as N-methylmorpholine may be added. Thisis followed by deprotection to give amino acid amide III. An amino acidester bearing R₂ and R₃ is then reacted with an acid chloride bearing R₁in the presence of a suitable base such as N,N-diisopropylethylamine.Conversion to the carboxylic acid provides IV. Standard peptide couplingof III and IV, followed by dehydration of the amide provides the desirednitrile II or IIa. An example of suitable dehydration conditions iscyanuric chloride in DMF.

[1003] In a variation (Method B) illustrated in Scheme II, an amino acidamide bearing R₆ is coupled with an amine-protected amino acid bearingR₂ and R₃. A suitable protecting group and coupling conditions would beas described above. Deprotection is then followed by reaction with anacid chloride bearing R₁. Conversion of the amide to the nitrile asabove provides II or IIa.

[1004] Compounds of the invention having formulas (I) or (Ia) (ketones)may be prepared by Methods C (Scheme III) or D (Scheme IV) as describedbelow.

[1005] According to Method C, a suitably protected (for example Bocprotected) amino acid is coupled with N,O-dimethylhydroxylamine understandard coupling conditions, such as with carbonyldiimidazole (CDI) ina solvent such as DMF, to give the corresponding amide. This is reducedto the aldehyde (V) with a suitable reducing agent such as LiAlH₄, in asuitable solvent such as THF.

[1006] The aldehyde (V) is reacted with the anion of a heterocycle R₈,which is generated by reacting R₈ with a strong base such as n-BuLi in asolvent such as THF at a temperature of about −30° C. to −100° C. andpreferably at about −78° C. This is followed by removal of theprotecting group providing alcohol (VI). This is coupled with (IV),prepared as described in Scheme I, under standard coupling conditionssuch as EDC and HOBT in DMF in the presence of a base such asN-methylmorpholine to provide (VII). Oxidation of (VII) with, forexample, the Dess Martin Reagent(1,1,1,-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one) in methylenechloride and t-BuOH, provides the desired ketone of formulas (I) or(Ia).

[1007] In Method D, a suitably protected amino acidN-methoxy-N-methylamide (prepared as described in Scheme III) is treatedwith the anion of a heterocycle R₈, generated by reacting R₈ with astrong base such as n-BuLi in a suitable solvent such as THF at atemperature of about −30° C. to −100° C. and preferably at about −78° C.Deprotection of the resulting ketone provides (VIII). This is coupledwith (IV), which is prepared as described in Scheme I, under standardcoupling conditions such as EDC and HOBT in DMF in the presence of abase such as N-methylmorpholine to provide the desired ketone offormulas (I) or (Ia).

[1008] Compounds of the invention where A is a bond (formulas I, Ia andII, Ia) could be prepared in analogous fashion to the Schemes above byusing R₁X, where X=Br, Cl, or I, instead of an acyl halide (R₁C(O)CI) inSchemes I and II, or by using R₁NHC(R₂)(R₃)CO₂H instead of (IV) inSchemes III and IV.

[1009] Intermediates used in Schemes I-IV are either commerciallyavailable or easily prepared by methods known to those skilled in theart. A procedure (Method E) that is useful for preparing substitutedoxazoles which may be used as R₈ in Scheme III and IV (Methods C and D)is illustrated below in Scheme V.

[1010] An N-protected amino acid, for example a t-Boc protected aminoacid (IX) is coupled with N,O-dimethylhydroxylamine using a suitablecoupling agent, such as carbonyldiimidazole (CDI), in a suitablesolvent, such as CH₂Cl₂, THF or DMF, at about 0° C. to provide (X). TheN-protecting group is then removed, for example the t-Boc group may beremoved by treatment with a suitable acid, such as trifluoroacetic acid,in a suitable solvent, such as CH₂Cl₂. The resulting amine is coupledwith the desired carboxylic acid using suitable coupling conditions,such as EDC with HOBT in a suitable solvent such as DMF, in the presenceof a base such as N-methylmorpholine to provide a diamide (XI). TheN-methoxy-methyl amide is then treated with a suitable reducing agent,such as LiAlH₄ in a suitable solvent, such as THF, to provide analdehyde (XII). Cyclodehydration (see for example P. Wipf and S. Lim, J.Amer. Chem. Soc., 1995, 117, 558) of (XII) with triphenylphosphine andhexachloroethane in a suitable solvent, such as acetonitrile in thepresence of a suitable base, such as Et₃N provides the desired oxazole(XIII).

[1011] Desired disubstituted thiazoles, which may be used as R₈ inScheme III and IV (Method C and D) may be prepared by the Hantzschmethod in which a thioamide is condensed with an alpha-halocarbonylcompound. This method is known to those skilled in the art and iswell-documented in the chemical literature (for example, J. Metzger andE. J. Vincent, The Chemistry of Heterocyclic Compounds, Vol. 34, 1979;A. R. Katritzky et al., J. Org. Chem., 1995, 60, 5638; R. Flaig and H.Hartmann, Heterocycles, 1997, 45, 875).

Methods of Therapeutic Use

[1012] The compounds of this invention effectively block degradation ofthe invariant chain to CLIP by cathepsin S, and thus inhibit antigenpresentation and antigen-specific immune responses. Control of antigenspecific immune responses is an attractive means for treating autoimmunediseases and other undesirable T-cell mediated immune responses. Thus,there is provided methods of treatment using the compounds of thisinvention for such conditions. These encompass autoimmune diseasesincluding, but not limited to, rheumatoid arthritis, systemic lupuserythematosus, Crohn's disease, ulcerative colitis, multiple sclerosis,Guillain-Barre syndrome, psoriasis, Grave's disease, myasthenia gravis,scleroderma, glomerulonephritis, atopic dermatitis and insulin-dependentdiabetes mellitus. The compounds of the invention can also be used totreat other disorders associated with extracellular proteolysis such asAlzheimer's disease. The compounds of the invention can also be used totreat other disorders associated with inappropriate autoimmuneresponses, T-cell mediated immune responses, or extracellularproteolysis mediated by cathepsin S, unrelated to those listed above ordiscussed in the Background of the Invention. Therefore, the inventionalso provides methods of modulating an autoimmune disease comprisingadministering to a patient in need of such treatment a pharmaceuticallyeffect amount of a compound according to the invention.

[1013] For therapeutic use, the compounds of the invention may beadministered in any conventional dosage form in any conventional manner.Routes of administration include, but are not limited to, intravenously,intramuscularly, subcutaneously, intrasynovially, by infusion,sublingually, transdermally, orally, topically or by inhalation. Thepreferred modes of administration are oral and intravenous.

[1014] The compounds of this invention may be administered alone or incombination with adjuvants that enhance stability of the inhibitors,facilitate administration of pharmaceutical compositions containing themin certain embodiments, provide increased dissolution or dispersion,increase inhibitory activity, provide adjunct therapy, and the like,including other active ingredients. Advantageously, such combinationtherapies utilize lower dosages of the conventional therapeutics, thusavoiding possible toxicity and adverse side effects incurred when thoseagents are used as monotherapies. Compounds of the invention may bephysically combined with the conventional therapeutics or otheradjuvants into a single pharmaceutical composition. Advantageously, thecompounds may then be administered together in a single dosage form. Insome embodiments, the pharmaceutical compositions comprising suchcombinations of compounds contain at least about 15%, but morepreferably at least about 20%, of a compound of formulas (I), (Ia), (II)or (IIa) (w/w) or a combination thereof. Alternatively, the compoundsmay be administered separately (either serially or in parallel).Separate dosing allows for greater flexibility in the dosing regime.

[1015] As mentioned above, dosage forms of the compounds of thisinvention include pharmaceutically acceptable carriers and adjuvantsknown to those of ordinary skill in the art. These carriers andadjuvants include, for example, ion exchangers, alumina, aluminumstearate, lecithin, serum proteins, buffer substances, water, salts orelectrolytes and cellulose-based substances. Preferred dosage formsinclude, tablet, capsule, caplet, liquid, solution, suspension,emulsion, lozenges, syrup, reconstitutable powder, granule, suppositoryand transdermal patch. Methods for preparing such dosage forms are known(see, for example, H. C. Ansel and N. G. Popovish, Pharmaceutical DosageForms and Drug Delivery Systems, 5th ed., Lea and Febiger (1990)).Dosage levels and requirements are well-recognized in the art and may beselected by those of ordinary skill in the art from available methodsand techniques suitable for a particular patient. In some embodiments,dosage levels range from about 10-1000 mg/dose for a 70 kg patient.Although one dose per day may be sufficient, up to 5 doses per day maybe given. For oral doses, up to 2000 mg/day may be required. As theskilled artisan will appreciate, lower or higher doses may be requireddepending on particular factors. For instance, specific dosage andtreatment regimens will depend on factors such as the patient's generalhealth profile, the severity and course of the patient's disorder ordisposition thereto, and the judgment of the treating physician.

SYNTHETIC EXAMPLES Example 1

[1016] Morpholine-4-carboxylic acid[1-(S)-(1-(S)-cyano-3-phenylpropylcarbamoyl)-3-methylbutyl]amide

[1017] As outlined generally in Scheme I (Method A),N-Boc-L-homophenylalanine (0.50 g, 1.79 mmol) was dissolved in 20 mL ofDMF which was cooled with an ice-water bath. 1-Hydroxybenzotriazole(HOBT) (0.29 g, 2.14 mmol) and EDC (0.41 g, 2.00 mmol) were addedfollowed by stirring for 20 min. Ammonium hydroxide was added (0.5 mL)and stirring was continued overnight (16 h). The reaction mixture wasdiluted with 50 mL of methylene chloride to give a white precipitate.The mixture was filtered and the filtrate was washed with brine (100 mL)followed by saturated bicarbonate (100 mL). The organic layer was driedover MgSO₄, filtered and concentrated by rotary evaporation to give thecorresponding amide (0.45 g, 90%) that was used without furtherpurification.

[1018] Benzyl L-leucine p-toluenesulfonate salt (8.00 g, 20.3 mmol) wasdissolved in 20 mL of DMF followed by addition ofN,N-diisopropylethylamine (10.61 mL, 60.9 mmol) and stirring under Arfor 15 min. 4-Morpholinecarbonyl chloride (4.55 g, 30.4 mmol) was addedand stirring was continued overnight (16 h). The solution was dilutedwith 500 mL of EtOAc and washed with 3×500 mL of water. The organiclayer was dried over MgSO₄, filtered and concentrated by rotaryevaporation to 8.01 g of the crude product. The product was purified byflash chromatography (SiO₂, 40% EtOAc/hexane) resulting in a thick oil.This oil (18 g, 53.8 mmol) was dissolved in ethanol (500 mL). Pd(OH)₂(642 mg) was added followed by cyclohexene (100 mL). The mixture wasrefluxed for 45 min at which time TLC indicated consumption of thebenzyl ester. The reaction was cooled and filtered through diatomaceousearth and evaporated to dryness to giveN-(4-morpholinecarbonyl)-L-leucine as a very thick oil (13 g, 99%) thatwas used without further purification.

[1019] N-Boc-L-homophenylalaninamide (from the first paragraph) (114 mg,0.41 mmol) was dissolved in 10 mL of CH₂Cl₂ and 10 mL of trifluoroaceticacid (TFA) was added. Stirring was continued for 30 min at which timethe reaction mixture was evaporated to dryness giving the TFA salt ofL-homophenylalanine amide. N-(4-morpholinecarbonyl)-L-leucine (100 mg,0.41 mmol), from above, was dissolved in 10 mL of DMF and cooled by anice-water bath. HOBT (72 mg, 0.53 mmol) and EDC (102 mg, 0.53 mmol) wereadded and the mixture was stirred at 0° C. for 15 min. To the coldsolution was added the TFA salt of L-homophenylalaninamide as a solutionin 5 mL of DMF, followed by addition of N-methylmorpholine (94 μL, 0.86mmol). The ice bath was removed and the reaction was stirred at ambienttemperature overnight (16 h). The reaction was diluted with 50 mL ofCH₂Cl₂ to give a white precipitate. The mixture was filtered and thesolid washed with an additional 50 mL of CH₂Cl₂. The filtrates werecombined and washed with saturated bicarbonate (100 mL), 1 N HCl (100mL) and brine (2×100 mL). The organic layer was dried over MgSO₄ andconcentrated by rotary evaporation to give an oily residue. The residuewas chromatographed (SiO₂, 5% MeOH in CH₂Cl₂) to give the a white solid(130 mg, 78%).

[1020] This amide (150 mg, 0.37 mmol) (material from more than onereaction) was dissolved in 2 mL of DMF and cooled to 0° C. with anice-water bath. To the solution was added cyanuric chloride (46 mg, 0.37mmol). The ice bath was removed and the reaction stirred to ambienttemperature over the next hour. During the course of the reaction awhite precipitate formed. The reaction was diluted with 100 mL of EtOAcand washed with 100 mL of water (3×). The organic layer was dried overMgSO₄, filtered and concentrated by rotary evaporation to give the cruderesidue. The residue was purified by chromatography (SiO₂, 40% hexane inEtOAc) to give the title compound as a hard white glass (120 mg, 84%).¹H NMR (270 MHz, CDCl₃): δ 8.00-7.87 (1H, m), 7.35-7.13 (3H, m),7.12-7.05 (2H, m), 5.10-5.02 (1H, m), 4.80-4.60 (1H, m), 4.45-4.20 (1H,m), 3.75-3.50 (4H, m), 3.45-3.30 (4H, m), 2.80-2.60 (2H, m), 2.10-1.90(2H, m), 1.70-1.45 (3H, m), 1.05-0.90 (6H, m).

Example 2

[1021] 2-(S)-(4-Dimethylaminobenzenesulfonylamino)-4-methylpentanoicacid (1-(S)-cyano-3-phenylpropyl) amide

[1022] NH₄OH (4 mL) was added to a premixed (15 min) solution ofN-(t-butoxycarbonyl)-L-homophenylalanine (4.00 g, 14.3 mmol), EDC (3.24g, 17.2 mmol), and HOBT (2.32 g, 17.2 mmol) in DMF (20 mL) at roomtemperature. After 16 h the reaction mixture was diluted with CH₂Cl₂ andfiltered, washed sequentially with 10% aqueous HCl, satd. NaHCO₃, H₂O(×3), brine, dried over Na₂SO₄, and concentrated givingN-(t-butoxycarbonyl)-L-homophenylalaninamide (3.10 g, 78%) as a whitesolid.

[1023] TFA (2.5 mL) was added to a solution ofN-(t-butoxycarbonyl)-L-homophenylalaninamide (1.00 g, 3.59 mmol) inCH₂Cl₂ (10 mL) at room temperature. After stirring for 0.5 h thereaction mixture was concentrated giving a colorless oil. As describedgenerally by Scheme II, Method B, the oil was dissolved in CH₂Cl₂ (10mL) and N,N-diisopropylethylamine (1.90 g, 14.4 mmol) and added to apremixed (15 min) solution of N-(t-butoxycarbonyl)-L-leucine (913 mg,3.95 mmol), EDC (826 mg, 4.30 mmol), HOBT (581 mg, 4.30 mmol) in CH₂Cl₂(10 mL) at room temperature. After stirring for 16 h the reaction wasquenched by the addition of H₂O, diluted with EtOAc, washed sequentiallywith 10% aqueous HCl, satd. NaHCO₃, H₂O brine, dried over Na₂SO₄, andconcentrated giving 1.3 g of a white solid. The crude solid wastriturated with 5%EtOAc/Hexane givingN-[N-(t-butoxycarbonyl)-L-leucinyl]-L-homophenylalaninamide (1.1 g, 78%)as a white solid.

[1024] TFA (2.5 mL) was added to a solution ofN-[N-(t-butoxycarbonyl)-L-leucinyl]-L-homophenylalaninamide (500 mg,1.28 mmol) in CH₂Cl₂ (10 mL) at room temperature. After stirring for 0.5h the reaction mixture was concentrated giving a colorless oil which wasdiluted with CH₂Cl₂ (2.5 mL). Diisopropylethylamine (588 mg, 4.55 mmol)and p-Me₂NC₆H₄SO₂Cl [prepared by the reaction of p-Me₂NC₆H₄SO₃ ⁻Na⁺ (1.0g, 4.48 mmol) with thionyl chloride and pyridine (1 mL) at 55° C. for 2h followed by cooling, diluting with toluene and concentrating to givep-Me₂NC₆H₄SO₂Cl.] was added at room temperature. After stirring for 16 hthe reaction was quenched by the addition of H₂O, diluted with EtOAc,washed sequentially with 10% aqueous HCl, satd. NaHCO₃, H₂O (×3), brine,dried over Na₂SO₄, and concentrated giving a yellow solid (408 mg). Thecrude residue was fractionated by flash chromatography (25-100%EtOAc/Hexane) givingN-[N-((4-dimethylaminophenyl)sulfonyl)-L-leucinyl]-L-homophenylalaninamide(90 mg, 15%) as a white solid. Some title compound (60 mg, 10%) wasisolated from this reaction as well.

[1025] Cyanuric chloride (33 mg, 0.18 mmol) was added to a solution ofN-[N-((4-dimethylaminophenyl)sulfonyl)-L-leucinyl]-L-homophenylalaninamide(80 mg, 0.18 mmol) in DMF (2 mL) at 0° C. After stirring for 2 h, thereaction was quenched by addition of satd. NaHCO₃, filtered, dilutedwith EtOAc, washed sequentially with H₂O (×5), brine, dried over Na₂SO₄,and concentrated giving a yellow foam. The crude residue wasfractionated by preparative HPLC (65% AcCN/H₂O/0.1%TFA) giving the titlecompound (47 mg, 57%) as a white solid, m.p. 46-48° C. ¹H NMR (400 MHz,CDCl₃): δ: 7.74(2H, d, J=9), 7.37-7.34 (2H, m), 7.30-7.26 (2H, m),7.23-7.21 (3H, m), 6.79 (1H, d, J=8.5), 4.91 (1H, bs), 4.70 (1H, ddd,J=8, 8, 8), 3.68-3.73 (1H, m), 3.06 (3H, s), 2.84-2.76 (2H, m),2.16-2.09(2H, m), 1.63-1.56 (2H, m), 1.42-1.37 (1H, m), 0.88 (3H, d,J=6), 0.71 (3H, d, J=6). 25

Example 3

[1026]2-(2-(S)-{4-Methyl-2-(S)-[(morpholine-4-carbonyl)amino]pentanoylamino}-4-phenylbutyryl)benzothiazole-6-carboxylicAcid Phenylamide

[1027] As described generally in Method C, N-(t-Boc)-L-homophenylalanine(10.0 g, 35.8 mmol) was dissolved in 50 mL of DMF. The solution wascooled to 0° C. with an ice-water bath. Carbonyldiimidazole (6.4 g, 39.4mmol) was added to the reaction solution followed by N-methylmorpholine(3.9 g, 39.4 mmol). The reaction was stirred for 1 h at which timeN,O-dimethylhydroxylamine hydrochloride (3.8 g, 39.4 mmol) was added.The ice bath was removed and the reaction was stirred at ambienttemperature for 3 h. The reaction solution was poured into 200 mL of 1NHCl and extracted with 200 mL of EtOAc. The organic layer was washedwith 2×100 mL of 1N HCl, 100 mL of saturated sodium bicarbonate, 2×100mL water, and 2×100 mL brine. The organic layer was dried over Na₂SO₄,decanted and concentrated by rotary evaporation to give the desiredamide as a thick oil (11.1 g, 96% crude) which was used without furtherpurification.

[1028] The amide (3.7 g, 11.5 mmol), dissolved in 20 mL THF was addeddropwise over 20 min to a suspension of LiAlH₄ (0.53 g, 13.9 mmol) in 60mL THF which was cooled to 0° C. in an ice-water bath. The mixture wasstirred for 15 min, then quenched with 10 mL of a saturated solution ofsodium bicarbonate, diluted with 200 mL water and extracted with 3×100mL EtOAc. The organic layers were combined and washed with 100 mL 1 NHCl and 2×100 mL brine. The organic layer was dried over Na₂SO₄,filtered over a pad of diatomaceous earth and concentrated by rotaryevaporation. The residue was purified by flash chromatography (SiO₂, 5%i-PrOH in CH₂Cl₂) to give the desired aldehyde as an oily solid (2.4 g,79%).

[1029] To a dry 100 mL flask was added 6-(phenylcarbamoyl)benzothiazole(0.58 g, 2.3 mmol) and THF (12 mL). The reaction mixture was cooled to−78° C. with a dry-ice/acetone bath. n-BuLi (2.5 M in hexanes) (1.8 mL,4.5 mmol) was added dropwise to the reaction mixture. The reaction wasstirred for 20 min to give a suspension. A solution of the abovealdehyde (200 mg, 0.75 mmol) in 3 mL of dry THF was added all at oncevia syringe. The temperature was gradually increased to 40° C. and thereaction was stirred for 3 h at which time TLC showed consumption of thealdehyde. The reaction was quenched at −78° C. by the addition of asaturated solution of NH₄Cl and the product was extracted with 50 mLEtOAc. The organic layer was dried over MgSO₄, filtered and concentratedto give a residue that was purified by chromatography (SiO₂, 2% MeOH inCH₂Cl₂) to give the desired alcohol as a solid (194 mg, 50%).

[1030] N-(4-morpholinecarbonyl)-L-leucine (26.4 mg, 0.11 mmol) (preparedas described in Example 1) was dissolved in 2 mL of DMF. The solutionwas cooled to 0° C. with an ice-water bath and HOBT (19 mg, 0.14 mmol)and EDC (27 mg, 0.14 mmol) were added and the solution stirred for 20min. The TFA salt of the N-deprotected alcohol from above (prepared bystirring the above N-Boc protected alcohol in methylene chloride withTFA at room temperature for 30 min and evaporation to dryness) (57 mg,0.11 mmol of N-Boc precursor) was added to the reaction as a solution in1 mL of DMF followed by addition of N-methylmorpholine (35 μL, 0.32mmol). The reaction was stirred for 3 h, diluted with EtOAc and washedwith 10 mL 1N HCl and 10 mL saturated bicarbonate and 2×100 mL brine.The organic layer was dried over MgSO₄, filtered and concentrated. Theresidue was purified by chromatography (SiO₂, 2% MeOH in CH₂Cl₂) to givethe desired coupled product as a white solid (57 mg, 82%).

[1031] To the above product (50.4 mg, 0.08 mmol) was added theDess-Martin periodinane (133 mg, 0.31 mmol), 10 mL CH₂Cl₂ and 4 mLt-BuOH. The reaction mixture was allowed to stir overnight at roomtemperature. It was then was diluted with 20 mL CH₂Cl₂, washed with 20mL of saturated solution of Na₂S₂O₃ and 20 mL Na₂CO₃ solution, theorganic layer was washed with brine, dried over MgSO₄, filtered andconcentrated. The residue was purified by chromatography (SiO₂, 2% MeOHin CH₂Cl₂) to give the title compound as a white solid (30 mg, 60%). H¹NMR (270 MHz, CDCl₃): δ 8.77-8.70 (1H, m), 8.57-8.52 (1H, m), 8.28-8.20(1H, m), 8.15-8.07 (1H, m), 7.78-7.68 (2H, m), 7.45-7.35 (2H, m),7.29-7.05 (7H, m), 5.75-5.65 (1H, m), 5.00-4.92 (1H, m), 4.54-4.41 (1H,m), 3.74-3.58 (4H, m), 3.40-3.24 (4H, m), 2.78-2.62 (2H, m), 2.51-2.32(1H, m), 2.21-2.02 (1H, m), 1.90-1.40 (3H, m), 1.00-0.80 (6H, m).

Example 4

[1032] Morpholine-4-carboxylic Acid{1-(S)-[1-(S)-(benzothiazole-2-carbonyl)-3-phenylpropylcarbamoyl]-3-methylbutyl}Amide

[1033] Dry THF (1.5 mL), under Ar, was cooled to −78° C. with adry-ice/acetone bath. n-BuLi (2.0 M in hexanes) (698 μL, 1.40 mmol) wasadded to reaction flask followed by dropwise addition of freshlydistilled benzothiazole (180 mg, 1.40 mmol) as a solution in 0.5 mL ofdry THF. The reaction was stirred for 15 min to give a suspension. Asolution ofN-(t-butoxycarbonyl)-(N′-methyl-N′-methoxy)-L-homophenylalaninamide (300mg, 0.930 mmol) (prepared as described in Example 3) in 1 mL of dry THFwas added all at once via syringe. The reaction was stirred for 5 min atwhich time TLC showed consumption of the amide. The reaction wasquenched by the addition of water and the product extracted with 50 mLof EtOAc. The organic layer was dried over MgSO₄, filtered andconcentrated to give a residue that was purified by preparative TLC(CH₂Cl₂) to give the desired ketone as a clear colorless oil.

[1034] N-(4-morpholinecarbonyl)-L-leucine (82 mg, 0.34 mmol) (preparedas described in Example 1) was dissolved in 2 mL of DMF. The solutionwas cooled to 0° C. with an ice-water bath and HOBT (60 mg, 0.44 mmol)and EDC (83 mg, 0.44 mmol) were added and the solution stirred for 20min. The TFA salt of the N-deprotected ketone from above (prepared bystirring the above N-Boc protected alcohol in methylene chloride withTFA at room temperature for 30 min and evaporation to dryness) (133 mg,0.34 mmol of N-Boc precursor) was added to the reaction as a solution in1 mL of DMF followed by addition of N-methylmorpholine (77 μL, 0.70mmol). The reaction was stirred for 3 h, diluted with EtOAc and washedwith 100 mL 1N HCl and 100 mL saturated bicarbonate and 2×100 mL brine.The organic layer was dried over MgSO₄, filtered and concentrated. Theresidue was purified by chromatography (SiO₂, 50% EtOAc in hexane) togive the title compound as a white solid (40 mg, 23%) that was shown tobe a 1 to 1 mixture of two epimers. ¹H NMR (270 MHz, CDCl₃): δ 8.15-8.08(1H, m), 7.98-7.88 (1H, m), 7.60-7.40 (2H, m), 7.25-7.07 (5H, m),7.02-6.92 (1H, m), 5.90-5.75 (1H, m), 4.98-4.90 (1H, m), 4.50-4.35 (1H,m), 3.66-3.57 (4H, m), 3.40-3.30 (4H, m), 2.80-2.70 (2H, m), 2.50-2.35(1H, m), 2.25-2.10 (1H, m), 1.80-1.40 (3H, m), 1.00-0.88 (6H, m).

Example 5

[1035] Morpholine-4-carboxylic Acid{1-(S)-[1-(S)-(2,4-diphenyloxazole-5-carbonyl)-3-phenylpropylcarbamoyl]-3-methylbutyl}amide

[1036] As outlined generally in Scheme IV (Method D),2,4-diphenyloxazole (361 mg, 1.63 mmol) in 15 mL dry THF was cooled to−78° C. and n-butyllithium (1.16 mL of a 1.4 M solution, 1.63 mmol) wasadded. After stirring for 1 h at −78° C., a solution of the free base ofN-[N-(t-butoxycarbonyl)-L-leucinyl]-L-homophenylalaninamide (prepared asdescribed in Example 3) in 5 mL of dry THF was added dropwise. Thetemperature of the reaction mixture was allowed to rise to −20° C. andmaintained for 2 h after which time the reaction mixture was quenchedwith 100 mL of NH₄Cl (10% aqueous) and extracted with 3×100 mL EtOAc.The combined extracts were washed with 2×100 mL brine, dried withNa₂SO₄, filtered and concentrated. The resulting residue was purified bychromatography (florisil, 15%-20% hexane in EtOAc) yielding 190 mg (72%)of [1-(2,4-diphenyloxazole-5-carbonyl)-3-phenylpropyl]carbamic acidtert-butyl ester.

[1037] N-[(4-Morpholinyl)carbonyl]-L-leucine (100 mg, 0.35 mmol)(prepared as described in Example 1) was dissolved in 10 mL DMF andcooled to 0° C. To the solution was added EDC (77 mg, 0.4 mmol) and HOBt(54 mg, 0.4 mmol) and the reaction was stirred for 1 h. In a separateflask, [1-(2,4-diphenyloxazole-5-carbonyl)-3-phenylpropyl]carbamic acidtert-butyl ester (158 mg, 0.31 mmol) was dissolved in 4 mL CH₂Cl₂ and 2mL TFA was added. After stirring for 1 h, the solvents were evaporated,the residue was dissolved in 5 mL DMF and N-methylmorpholine (406 mg,0.4 mmol) was added. The resulting solution was added to the previouslyprepared solution of activated leucine derivative at 0° C. The reactionmixture was stirred at room temperature for 3 h, cooled to 0° C., andquenched with 100 mL of a 10% solution of citric acid in water. Theresulting mixture was extracted with 3×100 mL EtOAc. The combinedorganic extracts were washed with 2×100 mL of saturated bicarbonate and1×100 mL brine. The organic layer was dried over Na₂SO₄, filtered andconcentrated to a residue that was purified by chromatography (florisil,30%-50% EtOAc in hexane) to give the title compound as a white solid (90mg, 84%), m.p. 83-5° C., MS (ES) 609 (M⁺).

[1038] The following compounds were also prepared using the proceduredescribed in Example 5:

[1039] Morpholine-4-carboxylic acid {1-(S)-[1(S)-(2,4-diphenyl-oxazole-5-carbonyl)-3-phenyl-propylcarbamoyl]-3,3-dimethylbutyl}amide, m.p. 95-7° C., MS (ES) 623 (M⁺).

[1040] Morpholine-4-carboxylic acid{2-cyclohexyl-1-(S)-[1-(S)-(2,4-diphenyl-oxazole-5-carbonyl)-3-phenyl-propylcarbamoyl]-ethyl}amide, m.p. 93-5° C., MS (ES) 649 (M⁺).

[1041] Morpholine-4-carboxylic acid{1-(S)-[2,4-diphenyl-oxazole-5-yl)-2-oxo-ethylcarbamoyl]-3-methylbutyl}amide, m.p. 155-7° C., MS (ES) 505 (M⁺).

[1042] Morpholine-4-carboxylic acid{2-cyclohexyl-1-(S)-[2-(2,4-diphenyl-oxazol-5-yl)-2-oxo-ethylcarbamoyl]-ethyl}-amide,m.p. 122-3° C., MS (ES) 545 (M⁺).

[1043] Morpholine-4-carboxylic acid{1-(S)-[2-(2,4-diphenyl-oxazol-5-yl)-2-oxo-ethylcarbamoyl]-3,3-dimethylbutyl}-amide,m.p. 97-9° C., MS (ES) 519 (M⁺).

[1044] Morpholine-4-carboxylic acid(1-(S)-{1-(S)-[2-(3-benzyloxy-phenyl)-oxazole-5-carbonyl]-3-phenyl-propylcarbamoyl}-3-methyl-butyl)-amide,m.p. 61-3° C., MS (ES) 639 (M⁺).

[1045] Morpholine-4-carboxylic acid {2-cyclohexyl-1-(S)-[1-(R,S)-(4-isobutyl-2-pyrinin-2-yl-oxazole-5-carbonyl)-3-phenyl-propylcarbamoyl]-ethyl}amide, m.p. 93-5° C., MS (ES) 649 (M⁺).

Example 6

[1046] 2-(4-Isobutyloxazol-2-yl)pyridine (Method E)

[1047] N-(t-Butoxy)-L-leucine (10 g, 43 mmol) was dissolved in 200 mL ofCH₂Cl₂. The solution was cooled to 0° C. with an ice-water bath.Carbonyldiimidazole (7.7 g, 47.5 mmol) was added and the reactionmixture was stirred for 1 h. N,O-dimethylhydroxylamine hydrochloride(4.64 g, 47.8 mmol) was added at 0° C. The ice bath was removed and thereaction was stirred at ambient temperature for 16 h. The reactionsolution was poured into 200 mL of an ice-cooled solution of 5% citricacid. The organic layer was separated, washed with 2×100 mL of 1N HCl,1×100 mL of saturated NaHCO₃, and 2×100 mL brine. The organic layer wasdried over Na₂SO₄, filtered, and concentrated by rotary evaporation togive [1-(N-methoxy-N-methylcarbamoyl)-3-methylbutyl]carbamic acidtert-butyl ester as a thick oil (7.39 g, 59% crude) which was usedwithout further purification.

[1048] The tert-butyl ester from above (1 g, 3.47 mmol) was dissolved in10 mL CH₂Cl₂ and 5 mL trifluoroacetic acid was added. The reactionmixture was stirred for 1 h. Solvents were evaporated and the residuewas taken up in 2×10 mL CH₂Cl₂ and evaporated to an oil. In a separateflask, picolinic acid (470 mg, 3.82 mmol) was dissolved in 10 mL DMF andthe resulting solution was cooled to 0° C. EDC (787 mg, 4.1 mmol) andHOBT (554 mg, 4.1 mmol) were added and the reaction mixture was stirredat 0° C. for 1 h. In a separate flask, the free amine prepared above wasdissolved in 5 mL DMF and 1.5 mL N-methylmorpholine was added. Thissolution was added to the reaction mixture at 0° C. The reaction mixturewas allowed to stir at ambient temperature for 16 h after which time itwas poured into a mixture of ice/5% citric acid (100 mL) and extractedwith 4×30 mL EtOAc. The combined EtOAc extracts were washed with 3×100mL brine, 2×100 mL NaHCO₃, 1×100 mL brine, dried with Na₂SO₄, andevaporated to an oil which was dried under vacuum yielding 990 mg (100%)of pyridine-2-carboxylic acid[1-(N-methoxy-N-methylcarbamoyl)-3-methylbutyl]amide. This was usedwithout further purification.

[1049] The amide from above (4.7 g, 14.7 mmol) was dissolved in 50 mLTHF and added to a slurry of LiAlH₄ (558 mg, 14.7 mmol) in 50 mL THF at−78° C. The reaction mixture was allowed to warm to 0° C. and maintainedfor 15 min, after which time it was cooled to −78° C. and cannulatedinto an ice-cooled solution of KHSO₄ (8.16 g, 60 mmol) in 200 mL H₂O.The resulting mixture was extracted with 5×100 mL EtOAc. The combinedextracts were washed with 2×100 mL satd.NaHCO₃ and 1×100 mL brine, driedwith Na₂SO₄ and evaporated to an oily residue which was flashchromatographed through SiO₂ (25% EtOAc/hexane-35% EtOAc/hexane)yielding 2.8 g (86%) of pyridine-2-carboxylic acid(1-formyl-3-methylbutyl)amide as a colorless oil which solidified onstanding.

[1050] Hexachloroethane (445 mg, 1.87 mmol) was dissolved in 5 mL CH₃CN.A solution of pyridine-2-carboxylic acid (1-formyl-3-methylbutyl)amide(137.5 mg, 0.625 mmol) in 2 mL CH₃CN was added followed by triethylamine(375 mg, 3.75 mmol) and triphenylphosphine (491 mg, 1.87 mmol). Theresulting mixture was stirred for ½ h, poured into brine, and extractedwith 2×25 mL EtOAc. The combined extracts were washed with 1×50 mLbrine, dried with Na₂SO₄ and evaporated to 665 mg of a tan solid whichwas flash chromatographed through SiO₂ (20%-35% hexane/EtOAc) yielding100 mg (76%) of the title compound as an amber oil, MS (ES) 203 (M⁺).

Assessment of Biological Properties

[1051] Expression and Purification of Recombinant Human Cathepsin S

[1052] Cloning of human cathepsin S:

[1053] U937 RNA was subjected to reverse transcriptase/polymerase chainreaction with primer A (5′cacaatgaaacggctggtttg 3′) and primer B(5′ctagatttctgggtaagaggg 3′) designed to specifically amplify thecathepsin S cDNA. The resulting 900 bp DNA fragment was subcloned intopGEM-T (Promega) and sequenced to confirm its identity. This constructwas used for all subsequent manipulations. This procedure is typical forcloning of known genes and is established in its field.

[1054] Human Pre-Pro-Cat S was removed from pGem-T vector (Promega, 2800Woods Hollow Rd, Madison, Wis. 53711) by digestion with restrictionenzyme SacII, followed by treatment with T4 DNA polymerase to generate ablunt end, and a second restriction enzyme digest with SalI. It wassubcloned into pFastBacl donor plasmid (GibcoBRL, 8717 Grovemont Cr.,Gaithersburg, Md. 20884) which had been cut with restriction enzymeBamH1 and blunt-ended and then cut with restriction enzyme SalI. Theligation mixture was used to transform DH5a competent cells (GibcoBRL)and plated on LB plates containing 100 ug/ml ampicillin. Colonies weregrown in overnight cultures of LB media containing 50 ug/ml Ampicillin,plasmid DNA isolated and correct insert confirmed by restriction enzymedigestion. Recombinant pFastBac donor plasmid was transformed intoDH10Bac competent cells (GibcoBRL). Large white colonies were pickedfrom LB plates containing 50 ug/ml kanamycin, 7 ug/ml gentamicin, 10ug/ml tetracycline, 100 ug/ml Bluo-gal, and 40 ug/ml IPTG. DNA wasisolated and used to transfect Sf9 insect cells using CellFECTIN reagent(GibcoBRL). Cells and supernatant were harvested after 72 hours. Viralsupernatant was passaged twice and presence of Cat S confirmed by PCR ofthe supernatant.

[1055] SF9 cells were infected with recombinant baculovirus at a MOI of5 for 48-72 hrs. Cell pellet was lysed and incubated in buffer at pH 4.5at 37 for 2 hours to activate Cat S from pro-form to active mature form(Bromme, D & McGrath, M., Protein Science, 1996, 5:789-791.) Presence ofCat S was confirmed by SDS-PAGE and Western blot using rabbit anti-humanproCat S.

[1056] Inhibition of Cathepsin S

[1057] Human recombinant cathepsin S expressed in Baculovirus is used ata final concentration of 101 nM in buffer. Buffer is 50 mM Na Acetate,pH 6.5, 2.5 mMEDTA, 2.5 mMTCEP. Enzyme is incubated with either compoundor DMSO for 10 min at 37C. Substrate 7-amino-4-methylcoumarin,CBZ-L-valyl-L-valyl-L-arginineamide (custom synthesis by MolecularProbes) is diluted to 20 uM in water (final concentration of 5 uM),added to assay and incubated for additional 10 minutes at 37 C. Compoundactivity is measured by diminished fluorescence compared to DMSO controlwhen read at 360 nm excitation and 460 nm emission.

[1058] Examples listed above were evaluated for inhibition of cathepsinS in the above assay. All had IC₅₀ of 100 micromolar or below.

[1059] The following prophetic compounds may be made in accordance withthe procedure outlined in Scheme IV (Method D), and the specific example5:

[1060] Morpholine-4-carboxylic acid{1-[2-(4-isobutyl-2-pyridin-2-yl-oxazol-5-yl)-2-oxo-ethylcarbamoyl]-3-methyl-butyl}-amide;

[1061] Morpholine-4-carboxylic acid{1-[2-(4-cyclohexylmethyl-2-pyridin-2-yl-oxazol-5-yl)-2-oxo-ethylcarbamoyl]-3-methyl-butyl}-amide;

[1062] Morpholine-4-carboxylic acid{1-[2-(4-cyclohexylmethyl-2-pyridin-3-yl-oxazol-5-yl)-2-oxo-ethylcarbamoyl]-3-methyl-butyl}-amide;

[1063] Morpholine-4-carboxylic acid{2-cyclohexyl-1-[2-(4-cyclohexylmethyl-2-pyridin-3-yl-oxazol-5-yl)-2-oxo-ethylcarbamoyl]-ethyl}-amide;

[1064] Morpholine-4-carboxylic acid{2-cyclohexyl-1-[2-(4-isobutyl-2-pyridin-3-yl-oxazol-5-yl)-2-oxo-ethylcarbamoyl]-ethyl}-amide;

[1065] Morpholine-4-carboxylic acid{1-[2-(4-isobutyl-2-pyridin-3-yl-oxazol-5-yl)-2-oxo-ethylcarbamoyl]-3-methyl-butyl}-amide;

[1066] Morpholine-4-carboxylic acid{1-[1-(4-isobutyl-2-pyridin-3-yl-oxazole-5-carbonyl)-3-phenyl-propylcarbamoyl]-3-methyl-butyl}-amide;

[1067] Morpholine-4-carboxylic acid{1-[1-(4-isobutyl-2-pyridin-3-yl-oxazole-5-carbonyl)-3-phenyl-propylcarbamoyl]-3,3-dimethyl-butyl}-amide;

[1068] Morpholine-4-carboxylic acid{1-[1-(4-isobutyl-2-pyridin-4-yl-oxazole-5-carbonyl)-3-phenyl-propylcarbamoyl]-3,3-dimethyl-butyl}-amide;

[1069] Morpholine-4-carboxylic acid{2-cyclohexyl-1-[1-(4-isobutyl-2-pyridin-4-yl-oxazole-5-carbonyl)-3-phenyl-propylcarbamoyl]-ethyl}-amide;

[1070] Morpholine-4-carboxylic acid{2-cyclohexyl-1-[1-(4-cyclohexylmethyl-2-pyridin-4-yl-oxazole-5-carbonyl)-3-phenyl-propylcarbamoyl]-ethyl}-amide;

[1071] Morpholine-4-carboxylic acid(2-cyclohexyl-1-{1-[4-isobutyl-2-(1-methylpiperidin-4-yl)-oxazole-5-carbonyl]-3-phenyl-propylcarbamoyl}-ethyl)-amide;

[1072] Morpholine-4-carboxylic acid(1-{1-[4-isobutyl-2-(1-methyl-piperidin-4-yl)-oxazole-5-carbonyl]-3-phenyl-propylcarbamoyl}-3,3-dimethyl-butyl)-amide;

[1073] Morpholine-4-carboxylic acid(1-{1-[4-isobutyl-2-(1-pyrimidin-2-yl-piperidin-4-yl)-oxazole-5-carbonyl]-3-phenyl-propylcarbamoyl}-3,3-dimethyl-butyl)-amide;

[1074] Morpholine-4-carboxylic acid(1-{2-[4-isobutyl-2-(1-pyrimidin-2-yl-piperidin-4-yl)-oxazol-5-yl]-2-oxo-ethylcarbamoyl}-3,3-dimethyl-butyl)-amide;

[1075] Morpholine-4-carboxylic acid(1-{2-[4-cyclohexylmethyl-2-(1-pyrimidin-2-yl-piperidin-4-yl)-oxazol-5-yl]-2-oxo-ethylcarbamoyl}-3-methyl-butyl)-amide;

[1076] Morpholine-4-carboxylic acid{1-[2-(4-cyclohexylmethyl-2-piperidin-3-yl-oxazol-5-yl)-2-oxo-ethylcarbamoyl]-3-methyl-butyl}-amide;

[1077] Morpholine-4-carboxylic acid{1-[2-(4-isobutyl-2-piperidin-3-yl-oxazol-5-yl)-2-oxo-ethylcarbamoyl]-3-methyl-butyl}-amide;

[1078] Morpholine-4-carboxylic acid(1-{2-[4-isobutyl-2-(1-methyl-piperidin-3-yl)-oxazol-5-yl]-2-oxo-ethylcarbamoyl}-3-methyl-butyl)-amide;

[1079] Morpholine-4-carboxylic acid(1-{2-[4-isobutyl-2-(1-methyl-piperidin-3-yl)-oxazol-5-yl]-2-oxo-ethylcarbamoyl}-3,3-dimethyl-butyl)-amide;

[1080] Morpholine-4-carboxylic acid(1-{2-[4-isobutyl-2-(1-methyl-piperidin-2-yl)-oxazol-5-yl]-2-oxo-ethylcarbamoyl}-3,3-dimethyl-butyl)-amide;

[1081] Morpholine-4-carboxylic acid(1-{1-[4-isobutyl-2-(1-methyl-piperidin-2-yl)-oxazole-5-carbonyl]-3-phenyl-propylcarbamoyl}-3-methyl-butyl)-amide;

[1082] Morpholine-4-carboxylic acid{1-[4-isobutyl-2-phenyl-oxazole-5-carbonyl)-3-phenyl-propylcarbamoyl]-3-methyl-butyl}-amide;

[1083] Morpholine-4-carboxylic acid{1-[1-(4-dimethylaminomethyl-2-phenyl-oxazole-5-carbonyl)-3-phenyl-propylcarbamoyl]-3-methyl-butyl}-amide;

[1084] Morpholine-4-carboxylic acid{1-[2-(4-dimethylaminomethyl-2-phenyl-oxazol-5-yl)-2-oxo-ethylcarbamoyl]-3-methyl-butyl}-amide;

[1085] Morpholine-4-carboxylic acid{2-cyclohexyl-1-[2-(4-dimethylaminomethyl-2-phenyl-oxazol-5-yl)-2-oxo-ethylcarbamoyl]-ethyl}-amide;

[1086] Morpholine-4-carboxylic acid{1-[2-(4-dimethylaminomethyl-2-phenyl-oxazol-5-yl)-2-oxo-ethylcarbamoyl]-3,3-dimethyl-butyl}-amide;

[1087] Morpholine-4-carboxylic acid{1-[1-(4-dimethylaminomethyl-2-phenyl-oxazol-5-carbonyl)-3-phenyl-propylcarbamoyl]-3,3-dimethyl-butyl}-amide;

[1088] Morpholine-4-carboxylic acid{1-[1-(4-hydroxymethyl-2-phenyl-oxazol-5-carbonyl)-3-phenyl-propylcarbamoyl]-3,3-dimethyl-butyl}-amide;

[1089] Morpholine-4-carboxylic acid(3,3-dimethyl-1-{2-[4-(4-methyl-piperazin-1-ylmethyl)-2-phenyl-oxazol-5-yl]-2-oxo-ethylcarbamoyl}-butyl)-amide;

[1090] Morpholine-4-carboxylic acid(3,3-dimethyl-1-{2-[4-(4-methyl-piperazin-1-ylmethyl)-2-pyridin-4-yl-oxazol-5-yl]-2-oxo-ethylcarbamoyl}-butyl)-amide;

[1091] Morpholine-4-carboxylic acid (3-methyl-1-{1[4-(4-methyl-piperazin-1-ylmethyl)-2-pyridin-4-yl-oxazole-5-carbonyl]-3-phenyl-propylcarbamoyl}-butyl)-amide;

[1092]{1-[4-Isobutyl-5-(2-{4-methyl-2-[(morpholine-4-carbonyl)-amino]-pentoylamino}-acetyl)-oxazol-2-yl]-3-methyl-butyl}carbamicacid benzyl ester;

[1093] Morpholine-4-carboxylic acid{2-cyclohexyl-1-[1-(4-isobutyl-2-pyrimidin-4-yl-oxazole-5-carbonyl)-3-phenyl-propylcarbamoyl]-ethyl}-amide;

[1094] Morpholine-4-carboxylic acid{2-cyclohexyl-1-[3-phenyl-1-(4-phenyl-2-pyridin-4-yl-thiazole-5-carbonyl)-propylcarbamoyl]-ethyl}-amide;and

[1095] Morpholine-4-carboxylic acid{2-cyclohexyl-1-[2-oxo-2-(2-pyridin-4-yl-4-p-tolyl-thiazole-5-yl)-ethylcarbamoyl]-ethyl}-amide.

[1096] Preferred prophetic compounds have S-stereochemistry at theirasymmetric carbons.

What is claimed is:
 1. A compound of formula (I):

wherein: A is —C(Y)— or —SO₂— Y is O, S or NR_(a) wherein R_(a) isselected from the group consisting of H, alkyl, aryl, alkoxy, aryloxy,alkylamino and arylamino; R₁ is thiomorpholinyl, piperidinyl,pyrrolidinyl, piperazinyl, furanyl, thienyl, pyridinyl, pyridazinyl,pyrimidinyl, pyrazinyl, indolyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyl orphenoxazinyl wherein R₁ is unsubstituted or substituted by one or moreR_(b); R_(b) is selected from the group consisting of alkyl, cycloalkyl,aryl, heterocyclyl, heteroaryl, alkoxy, aryloxy, alkoxycarbonyl,aryloxycarbonyl, alkanoyl, aroyl, alkanoyloxy, aroyloxy, carbamoylwherein the nitrogen atom is unsubstituted or independently mono ordi-substituted by alkyl, aryl, heterocyclyl or heteroaryl,alkanoylamino, aroylamino, alkylthio wherein the sulfur atom isunoxidized or oxidized to a sulfoxide or sulfone, arylthio wherein thesulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, ureidowherein either nitrogen atom is unsubstituted or independentlysubstituted by alkyl, aryl, heterocyclyl or heteroaryl,alkoxycarbonylamino, aryloxycarbonylamino, alkylcarbamoyloxy,arylcarbamoyloxy, alkylsulfonylamino, arylsulfonylamino,alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atomis unsubstituted or independently mono or di-substituted by alkyl, aryl,heterocyclyl or heteroaryl, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino, R_(b) is unsubstituted or substituted byone or more R_(c); R_(c) is selected from the group consisting of alkyl,cycloalkyl, aryl, heterocycle, heteroaryl, arylalkyl, alkoxy, aryloxy,arylalkoxy, alkanoyl, aroyl, amino wherein the nitrogen atom isunsubstituted or independently mono or di-substituted by alkyl, aryl,heterocyclyl or heteroaryl, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino; R₂ is H or alkyl; R₃ is H, alkyl,cycloalkyl, aryl, heterocyclyl or heteroaryl, wherein R₃ isunsubstituted or substituted by one or more groups of the formula R_(d);R_(d) is selected from the group consisting of alkyl, cycloalkyl, aryl,heterocyclyl, heteroaryl, alkoxy, aryloxy, arylalkoxy, alkoxycarbonyl,aryloxycarbonyl, alkanoyl, aroyl, alkanoyloxy, aroyloxy, carbamoylwherein the nitrogen atom is unsubstituted or independently mono ordi-substituted by alkyl, aryl, heterocyclyl or heteroaryl,alkanoylamino, aroylamino, alkylthio wherein the sulfur atom isunoxidized or oxidized to a sulfoxide or sulfone, arylthio wherein thesulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, ureidowherein either nitrogen atom is unsubstituted or independentlysubstituted by alkyl, aryl, heterocyclyl or heteroaryl,alkoxycarbonylamino, aryloxycarbonylamino, alkylcarbamoyloxy,arylcarbamoyloxy, alkylsulfonylamino, arylsulfonylamino,alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atomis unsubstituted or independently mono or di-substituted by alkyl, aryl,heterocyclyl or heteroaryl, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino, R_(d) is unsubstituted or substituted byone or more R_(e); R_(e) is selected from the group consisting of alkyl,cycloalkyl, aryl, arylalkyl, alkoxy, aryloxy, arylalkoxy, alkanoyl,aroyl, amino, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino andguanidino; R₄ is H or alkyl; R₅ is H, alkyl or cycloalkyl; R₆ is H,alkyl, cycloalkyl, aryl, heterocyclyl or heteroaryl, wherein R₆ isunsubstituted or substituted by one or more groups of the formula R_(f);R_(f) is selected from the group consisting of alkyl, cycloalkyl, aryl,heterocyclyl, heteroaryl, alkoxy, aryloxy, alkanoyl, aroyl, arylalkoxy,heteroarylalkoxy, alkoxycarbonyl, aryloxycarbonyl, alkanoyloxy,aroyloxy, carbamoyl wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by alkyl, aryl, heterocyclyl orheteroaryl, alkanoylamino, aroylamino, alkylthio wherein the sulfur atomis unoxidized or oxidized to a sulfoxide or sulfone, arylthio whereinthe sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone,arylalkylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, ureido wherein either nitrogen atom isunsubstituted or independently substituted by alkyl, aryl, heterocyclylor heteroaryl, alkoxycarbonylamino, aryloxycarbonylamino,alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino,arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino whereinthe nitrogen atom is unsubstituted or independently mono ordi-substituted by alkyl, aryl, heterocyclyl or heteroaryl, halogen,hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino, R_(f) isunsubstituted or substituted by one or more R_(g); R_(g) is selectedfrom the group consisting of alkyl, cycloalkyl, aryl unsubstituted orsubstituted by halogen, C1-5alkyl or C1-5alkoxy, heterocyclyl,heteroaryl, alkoxy, aryloxy, arylalkoxy, alkoxycarbonyl,aryloxycarbonyl, alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogenatom is unsubstituted or independently mono or di-substituted by alkyl,aryl, heterocyclyl or heteroaryl; alkanoylamino, aroylamino, alkylthiowherein the sulfur atom is unoxidized or oxidized to a sulfoxide orsulfone, arylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, ureido wherein either nitrogen atom isunsubstituted or independently substituted by alkyl, aryl, heterocyclylor heteroaryl; alkoxycarbonylamino, aryloxycarbonylamino,alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino,arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino whereinthe nitrogen atom is unsubstituted or independently mono ordi-substituted by alkyl, aryl, heterocyclyl or heteroaryl; halogen,hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino; or R₅together with R₆ form a 3 to 6 membered carbocyclic ring, thecarbocyclic ring being unsubstituted or substituted with one or moreR_(h); R_(h) is selected from the group consisting of alkyl, aryl,alkoxycarbonyl, aryloxycarbonyl, arylalkoxycarbonyl, carbamoyl whereinthe nitrogen atom is unsubstituted or mono or di-substituted by alkyl,cycloalkyl, aryl, arylalkyl, heterocyclyl or heteroaryl; halogen,hydroxy, carboxy and cyano; R₇ is R₈—C(Z)-; wherein Z is O, S, or NR_(i)wherein R_(i) is selected from the group consisting of H, alkyl, aryl,alkoxy, aryloxy and hydroxy; R₈ is a heteroaryl ring selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, pyridyl, pyridazinyl,pyrimidinyl, pyrazinyl, triazinyl, indolizinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, triazolyl, tetrazolyl, purinyl, quinolizinyl, quinolinyl,isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl,naphthyridinyl, pteridinyl, carbazolyl, acridinyl and phenazinyl,wherein any of the above R₈ can be unsubstituted or substituted by oneor more R_(j); R_(j) is selected from the group consisting of alkyl,cycloalkyl, aryl, heterocyclyl, heteroaryl, arylalkyl, alkoxy, aryloxy,alkanoyl, aroyl, arylalkoxy, alkoxycarbonyl, aryloxycarbonyl,alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom isunsubstituted or independently mono or di-substituted by alkyl, aryl,heterocyclyl or heteroaryl, alkanoylamino, aroylamino, alkylthio whereinthe sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone,arylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, arylalkylthio wherein the sulfur atom isunoxidized or oxidized to a sulfoxide or sulfone, ureido wherein eithernitrogen atom is unsubstituted or independently substituted by alkyl,aryl, heterocyclyl or heteroaryl; alkoxycarbonylamino,aryloxycarbonylamino, alkylcarbamoyloxy, arylcarbamoyloxy,alkylsulfonylamino, arylsulfonylamino, alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by alkyl, aryl, heterocyclyl orheteroaryl; halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino andguanidino, R_(j) is unsubstituted or substituted by one or more R_(k);R_(k) is selected from the group consisting of alkyl, cycloalkyl, aryl,heterocyclyl, heteroaryl, alkoxy, aryloxy, arylalkoxy, alkoxycarbonyl,aryloxycarbonyl, alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogenatom is unsubstituted or independently mono or di-substituted by alkyl,aryl, heterocyclyl or heteroaryl, alkanoylamino, aroylamino, alkylthiowherein the sulfur atom is unoxidized or oxidized to a sulfoxide orsulfone, arylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, ureido wherein either nitrogen atom isunsubstituted or independently substituted by alkyl, aryl, heterocyclylor heteroaryl, alkoxycarbonylamino, aryloxycarbonylamino,arylalkoxycarbonylamino, arylalkoxycarbonylaminoalkyl,alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino,arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino whereinthe nitrogen atom is unsubstituted or independently mono ordi-substituted by alkyl, aryl, heterocyclyl or heteroaryl, halogen,hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino; and X is O,S or N—OH; or the pharmaceutically acceptable salts, esters, tautomers,individual isomers and mixtures of isomers thereof; with the provisothat when R₆ is alkyl the alkyl must be substituted with R_(f) whereinR_(f) is not hydroxy, sulfhydryl or halogen.
 2. The compound accordingto claim 1 wherein: R_(a) is selected from the group consisting of H,alkyl and aryl; R_(b) is selected from the group consisting of C1-8alkyl, C3-7 cycloalkyl, aryl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl; heteroaryl selected from the group consistingof furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl,isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl,thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl,isoindolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, purinyl, quinolinyl, isoquinolinyl, quinazolinyl,quinoxalinyl, carbazolyl, phenothiazinyl and phenoxazinyl, C1-8 alkoxy,aryloxy, C1-8 alkoxycarbonyl, aryloxycarbonyl, C1-8 alkanoyloxy,aroyloxy, carbamoyl wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by C1-8 alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl,triazolyl, tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl,pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, C1-8 alkanoylamino, aroylamino, C1-8 alkylthio whereinthe sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone,arylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, ureido wherein either nitrogen atom isunsubstituted or independently substituted by alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl,triazolyl, tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl,pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, alkoxycarbonylamino, aryloxycarbonylamino, C1-8alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino,arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino whereinthe nitrogen atom is unsubstituted or independently mono ordi-substituted by alkyl, aryl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl, or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidinoand guanidino, R_(b) is unsubstituted or substituted by one or moreR_(c); R_(c) is selected from the group consisting of C1-8 alkyl, C3-6cycloalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, C1-8 alkoxy, aryloxy,halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino; R₃is H, C1-8 alkyl, C3-7 cycloalkyl or aryl wherein R₃ is unsubstituted orsubstituted by one or more R_(d); R_(d) is selected from the groupconsisting of C1-8 alkyl, C3-7 cycloalkyl, aryl, heterocyclyl selectedfrom the group consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl; heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, C1-8 alkoxy, aryloxy, alkanoyl, aroyl, C1-8alkoxycarbonyl, aryloxycarbonyl, C1-8 alkanoyloxy, aroyloxy, carbamoylwherein the nitrogen atom is unsubstituted or independently mono ordi-substituted by C1-8 alkyl, aryl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl, or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, C1-8 alkanoylamino, aroylamino, C1-8 alkylthio whereinthe sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone,arylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, ureido wherein either nitrogen atom isunsubstituted or independently substituted by alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl,triazolyl, tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl,pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, alkoxycarbonylamino, aryloxycarbonylamino, C1-8alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino,arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino whereinthe nitrogen atom is unsubstituted or independently mono ordi-substituted by alkyl, aryl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidinoand guanidino, R_(d) is unsubstituted or substituted by one or moreR_(e); R_(e) is selected from the group consisting of C1-8 alkyl, C3-6cycloalkyl, aryl, arylalkyl, C1-8 alkoxy, aryloxy, arylalkoxy, aroyl,amino, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino andguanidino; R₅ is H or alkyl; R₆ is H, C1-8 alkyl, C3-7 cycloalkyl oraryl wherein R₆ is unsubstituted or substituted by one or more R_(f);R_(f) is selected from the group consisting of C1-8 alkyl, C3-7cycloalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, C1-8 alkoxy, aryloxy,arylC1-8alkoxy, heteroarylC1-8alkoxy, C1-8 alkoxycarbonyl,aryloxycarbonyl, C1-8 alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom is unsubstituted or independently mono or di-substitutedby C1-8 alkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl, or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, C1-8 alkanoylamino,aroylamino, C1-8 alkylthio wherein the sulfur atom is unoxidized oroxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom isunoxidized or oxidized to a sulfoxide or sulfone, arylC1-8 alkylthiowherein the sulfur atom is unoxidized or oxidized to a sulfoxide orsulfone, ureido wherein either nitrogen atom is unsubstituted orindependently substituted by alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, alkoxycarbonylamino, aryloxycarbonylamino, C1-8alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino,arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino whereinthe nitrogen atom is unsubstituted or independently mono ordi-substituted by alkyl, aryl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidinoand guanidino, R_(f) is unsubstituted or substituted by one or moreR_(g); R_(g) is selected from the group consisting of C1-8 alkyl, C3-7cycloalkyl, aryl unsubstituted or substituted by halogen, C1-3alkyl orC1-3alkoxy; heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, C1-8 alkoxy, aryloxy,arylC1-8alkoxy, C1-8 alkoxycarbonyl, aryloxycarbonyl, C1-8 alkanoyloxy,aroyloxy, carbamoyl wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by C1-8 alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl,triazolyl, tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl,pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, C1-8 alkanoylamino, aroylamino, C1-8 alkylthio whereinthe sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone,arylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, ureido wherein either nitrogen atom isunsubstituted or independently substituted by alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl,triazolyl, tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl,pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, alkoxycarbonylamino, aryloxycarbonylamino, C1-8alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino,arylsulfonylamino, alkylaminosulfonyl and arylaminosulfonyl, aminowherein the nitrogen atom is unsubstituted or independently mono ordi-substituted by alkyl, aryl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl, or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidinoand guanidino; R_(h) is selected from the group consisting of C1-8alkyl, aryl, C1-8 alkoxycarbonyl, aryloxycarbonyl,arylC1-8alkoxycarbonyl, carbamoyl wherein the nitrogen atom isunsubstituted or mono or di-substituted by C1-8 alkyl, C3-7 cycloalkyl,aryl, arylC1-8alkyl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl, or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, halogen, hydroxy, carboxyand cyano; R_(j) is selected from the group consisting of alkyl,cycloalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, arylalkyl, alkoxy, aryloxy,arylalkoxy, alkoxycarbonyl, aryloxycarbonyl, alkanoyloxy, aroyloxy,carbamoyl wherein the nitrogen atom is unsubstituted or independentlymono or di-substituted by alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl, or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, alkanoylamino, aroylamino, alkylthio wherein thesulfur atom is unoxidized or oxidized to a sulfoxide or sulfone,arylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, arylalkylthio wherein the sulfur atom isunoxidized or oxidized to a sulfoxide or sulfone, ureido wherein eithernitrogen atom is unsubstituted or independently substituted by alkyl,aryl, heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl,oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyridinyl,pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl and phenoxazinyl, alkoxycarbonylamino,aryloxycarbonylamino, C1-8 alkylcarbamoyloxy, arylcarbamoyloxy,alkylsulfonylamino, arylsulfonylamino, alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl,triazolyl, tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl,pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidinoand guanidino, R_(j) is unsubstituted or substituted by one or moreR_(k); R_(k) is selected from the group consisting of alkyl, cycloalkyl,aryl, heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl;heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl,oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyridinyl,pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl and phenoxazinyl, alkoxy, aryloxy, arylalkoxy,alkoxycarbonyl, aryloxycarbonyl, alkanoyloxy, aroyloxy, carbamoylwherein the nitrogen atom is unsubstituted or independently mono ordi-substituted by alkyl, aryl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, alkanoylamino, aroylamino, alkylthio wherein thesulfur atom is unoxidized or oxidized to a sulfoxide or sulfone,arylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, ureido wherein either nitrogen atom isunsubstituted or independently substituted by alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl,triazolyl, tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl,pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, alkoxycarbonylamino, aryloxycarbonylamino,arylalkoxycarbonylamino, arylalkoxycarbonylaminoalkyl, C1-8alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino,arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino whereinthe nitrogen atom is unsubstituted or independently mono ordi-substituted by alkyl, aryl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidinoand guanidino; and X is O or S.
 3. The compound according to claim 2wherein: Y is O or S; R₁ is pyrrolidinyl, piperidinyl, thiomorpholinyl,piperazinyl, furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, quinolinyl, isoquinolinyl, quinazolinyl or quinoxalinylwherein R₁ is unsubstituted or substituted by one or more R_(b); R_(b)is selected from the group consisting of C1-5 alkyl, C3-7 cycloalkyl,phenyl, naphthyl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl, heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl,tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl,isoquinolinyl, quinazolinyl and quinoxalinyl, C1-5 alkoxy, aryloxy, C1-5alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoylwherein the nitrogen atom is unsubstituted or independently mono ordi-substituted by C1-8 alkyl, aryl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, quinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl,C1-5 alkanoylamino, aroylamino, C1-5 alkylthio wherein the sulfur atomis unoxidized or oxidized to a sulfoxide or sulfone, arylthio whereinthe sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone,ureido wherein either nitrogen atom is unsubstituted or independentlysubstituted by alkyl, aryl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, quinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl,C1-5 alkoxycarbonylamino, aryloxycarbonylamino, C1-5 alkylcarbamoyloxy,arylcarbamoyloxy, C1-5 alkylsulfonylamino, arylsulfonylamino, C1-5alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atomis unsubstituted or independently mono or di-substituted by alkyl, aryl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl,pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino, R_(b) is unsubstituted or substituted byone or more R_(c); R_(c) is selected from the group consisting of C1-5alkyl, C3-6 cycloalkyl, aryl, heterocyclyl selected from the groupconsisting of piperidinyl, morpholinyl and piperazinyl; heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, tetrazolyl and pyridinyl, C1-5 alkoxy,aryloxy, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino andguanidino; R₂ is H or C1-3 alkyl; R₃ is H, C1-5 alkyl, C3-7 cycloalkylor aryl, wherein R₃ is unsubstituted or substituted by one or moreR_(d); R_(d) is selected from the group consisting of C1-5 alkyl, C3-7cycloalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl,tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl,isoquinolinyl, quinazolinyl and quinoxalinyl, C1-5 alkoxy, aryloxy,C1-5alkanoyl, aroyl, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom isunsubstituted or independently mono or di-substituted by C1-5 alkyl,aryl, heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl,pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, C1-5 alkanoylamino, aroylamino, C1-5alkylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, arylthio wherein the sulfur atom is unoxidized oroxidized to a sulfoxide or sulfone, ureido wherein either nitrogen atomis unsubstituted or independently substituted by C1-5 alkyl, aryl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl orheteroaryl selected the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl,pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, C1-5 alkoxycarbonylamino,aryloxycarbonylamino, C1-5 alkylcarbamoyloxy, arylcarbamoyloxy, C1-5alkylsulfonylamino, arylsulfonylamino, C1-5 alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by C1-5 alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl,pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino, R_(d) is unsubstituted or substituted byone or more R_(e); R_(e) is selected from the group consisting of C1-5alkyl, C3-6 cycloalkyl, aryl, arylalkyl, C1-5 alkoxy, aryloxy,arylC1-5alkoxy, aroyl, amino, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino; R₄ is H or C1-3 alkyl; R₅ is H or C1-8alkyl; R₆ is H, C1-5 alkyl, C3-7 cycloalkyl or aryl wherein R₆ isunsubstituted or substituted by one or more R_(f); R_(f) is selectedfrom the group consisting of C1-5 alkyl, C3-7 cycloalkyl, aryl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl;heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl,pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, C1-5 alkoxy, aryloxy, arylC1-5alkoxy,heteroarylC1-5alkoxy, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom isunsubstituted or independently mono or di-substituted by C1-5 alkyl,aryl, heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl,pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, C1-5 alkanoylamino, aroylamino, C1-5alkylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, arylthio wherein the sulfur atom is unoxidized oroxidized to a sulfoxide or sulfone, arylC1-5 alkylthio wherein thesulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, ureidowherein either nitrogen atom is unsubstituted or independentlysubstituted by C1-5 alkyl, aryl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, quinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl,C1-5 alkoxycarbonylamino, aryloxycarbonylamino, C1-5 alkylcarbamoyloxy,arylcarbamoyloxy, C1-5 alkylsulfonylamino, arylsulfonylamino, C1-5alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atomis unsubstituted or independently mono or di-substituted by C1-5 alkyl,aryl, heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl,pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino, R_(f) is unsubstituted or substituted byone or more R_(g); R_(g) is selected from the group consisting of C1-5alkyl, C3-7 cycloalkyl, aryl unsubstituted or substituted by halogen,methyl or methoxy; heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl,tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl,isoquinolinyl, quinazolinyl and quinoxalinyl, C1-5 alkoxy, aryloxy,arylC1-5alkoxy, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy,aroyloxy, carbamoyl wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by C1-5 alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl,pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, C1-5 alkanoylamino, aroylamino, C1-5alkylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, arylthio wherein the sulfur atom is unoxidized oroxidized to a sulfoxide or sulfone, ureido wherein either nitrogen atomis unsubstituted or independently substituted by C1-5 alkyl, aryl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl,pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, C1-5 alkoxycarbonylamino,aryloxycarbonylamino, C1-5 alkylcarbamoyloxy, arylcarbamoyloxy, C1-5alkylsulfonylamino, arylsulfonylamino, C1-5 alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by C1-5 alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl,pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino; R_(h) is selected from the groupconsisting of C1-5 alkyl, aryl, C1-5 alkoxycarbonyl, aryloxycarbonyl,arylC1-5alkoxycarbonyl, carbamoyl wherein the nitrogen atom isunsubstituted or mono or di-substituted by C1-5 alkyl, C3-7 cycloalkyl,aryl, arylC1-5alkyl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl,tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl,isoquinolinyl, quinazolinyl and quinoxalinyl, halogen, hydroxy, carboxyand cyano; R₁ is alkoxy, aryloxy or hydroxy; R₈ is a heteroaryl ringselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl,pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, indolizinyl,indolyl, isoindolyl, benzofuranyl, benzothienyl, indazolyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolizinyl,quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl,quinoxalinyl, naphthyridinyl, pteridinyl, carbazolyl, acridinyl andphenazinyl, wherein any of the above R₈ can be unsubstituted orsubstituted by one or more R_(j); R_(j) is selected from the groupconsisting of C1-8alkyl, C3-7cycloalkyl, aryl, heterocyclyl selectedfrom the group consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl; heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl; arylC1-8alkyl, C1-8alkoxy, aryloxy, arylC1-8alkoxy,C1-8alkoxycarbonyl, aryloxycarbonyl, C1-8alkanoyloxy, aroyloxy,carbamoyl wherein the nitrogen atom is unsubstituted or independentlymono or di-substituted by C1-8alkyl, aryl, heterocyclyl selected fromthe group consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl, or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, C1-8alkanoylamino, aroylamino, C1-8alkylthio whereinthe sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone,arylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, arylC1-8alkylthio wherein the sulfur atom isunoxidized or oxidized to a sulfoxide or sulfone, ureido wherein eithernitrogen atom is unsubstituted or independently substituted by C1-8alkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl, or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, alkoxycarbonylamino,aryloxycarbonylamino, C1-8 alkylcarbamoyloxy, arylcarbamoyloxy,alkylsulfonylamino, arylsulfonylamino, alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by C1-8 alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl,triazolyl, tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl,pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidinoand guanidino, R_(j) is unsubstituted or substituted by one or moreR_(k); R_(k) is selected from the group consisting of C1-8 alkyl, C3-7cycloalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl, heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, C1-8 alkoxy, aryloxy,arylC1-8alkoxy, C1-8alkoxycarbonyl, aryloxycarbonyl, C1-8alkanoyloxy,aroyloxy, carbamoyl wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by C1-8alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl,triazolyl, tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl,pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, alkanoylamino, aroylamino, C1-8alkylthio wherein thesulfur atom is unoxidized or oxidized to a sulfoxide or sulfone,arylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, ureido wherein either nitrogen atom isunsubstituted or independently substituted by C1-8alkyl, aryl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl,oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyridinyl,pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl and phenoxazinyl, C1-8alkoxycarbonylamino,aryloxycarbonylamino, arylC1-8alkoxycarbonylamino,arylalkoxycarbonylaminoC1-8alkyl, C1-8 alkylcarbamoyloxy,arylcarbamoyloxy, C1-8alkylsulfonylamino, arylsulfonylamino,C1-8alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogenatom is unsubstituted or independently mono or di-substituted byC1-8alkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl, or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, halogen, hydroxy, oxo,carboxy, cyano, nitro, amidino and guanidino.
 4. The compound accordingto claim 3 wherein: Y is O; R₁ is piperidinyl, thiomorpholinyl,piperazinyl, furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl orisoquinolinyl, wherein R₁ is unsubstituted or substituted by one or moreR_(b); R_(b) is selected from the group consisting of C1-5 alkyl, C3-7cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl; heteroaryl selected from the group consistingof furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl,tetrazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl andisoquinolinyl; C1-5 alkoxy, aryloxy, C1-5 alkoxycarbonyl,aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom is unsubstituted or independently mono or di-substitutedby C1-5 alkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl andindolinyl, or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, tetrazolyl,pyridinyl, indolyl, benzofuranyl, benzothienyl, benzimidazolyl,benzthiazolyl, benzoxazolyl, quinolinyl and isoquinolinyl, C1-5alkanoylamino, aroylamino, C1-5 alkylthio wherein the sulfur atom isunoxidized or oxidized to a sulfoxide or sulfone, arylthio wherein thesulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, ureidowherein either nitrogen atom is unsubstituted or independentlysubstituted by alkyl or aryl; C1-5 alkoxycarbonylamino,aryloxycarbonylamino, C1-5 alkylcarbamoyloxy, arylcarbamoyloxy, C1-5alkylsulfonylamino, arylsulfonylamino, C1-5 alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyland isoquinolinyl, halogen, hydroxy, oxo, carboxy, cyano and nitro,R_(b) is unsubstituted or substituted by one or more R_(c); R_(c) isselected from the group consisting of C1-5 alkyl, C3-6 cycloalkyl, aryl,C1-5 alkoxy, aryloxy, halogen, hydroxy, oxo, carboxy, and cyano; R₂ is Hor methyl; R₃ is H, C1-5 alkyl, C3-7 cycloalkyl or phenyl, wherein R₃ isunsubstituted or substituted by one or more R_(d); R_(d) is selectedfrom the group consisting of C1-3 alkyl, C3-6 cycloalkyl, phenyl,naphthyl, heterocyclyl selected from the group consisting ofpiperidinyl, morpholinyl and piperazinyl; heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl andisoquinolinyl, C1-5 alkoxy, aryloxy, aroyl, C1-5 alkoxycarbonyl,aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom is unsubstituted or independently mono or di-substitutedby C1-5 alkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl and piperazinyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyland isoquinolinyl, C1-5 alkanoylamino, aroylamino, C1-5 alkylthiowherein the sulfur atom is unoxidized or oxidized to a sulfoxide orsulfone, arylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, ureido wherein either nitrogen atom isunsubstituted or independently substituted by C1-5 alkyl, phenyl,naphthyl, heterocyclyl selected from the group consisting ofpiperidinyl, morpholinyl and piperazinyl or heteroaryl selected thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl andisoquinolinyl, C1-5 alkoxycarbonylamino, aryloxycarbonylamino, C1-5alkylcarbamoyloxy, arylcarbamoyloxy, C1-5 alkylsulfonylamino,arylsulfonylamino, C1-5 alkylaminosulfonyl, arylaminosulfonyl, aminowherein the nitrogen atom is unsubstituted or independently mono ordi-substituted by C1-5 alkyl, phenyl, naphthyl, heterocyclyl selectedfrom the group consisting of piperidinyl, morpholinyl and piperazinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,quinolinyl and isoquinolinyl, halogen, hydroxy, oxo, carboxy and cyano,R_(d) is unsubstituted or substituted by one or more R_(e); R_(e) isselected from the group consisting of C1-5 alkyl, C3-6 cycloalkyl, aryl,arylC1-5alkyl, C1-5 alkoxy, aryloxy, arylC1-3alkoxy, aroyl, amino,halogen, hydroxy, oxo, carboxy and cyano; R₄ is H or methyl; R₅ is H orC1-5 alkyl; R₆ is H, C1-5 alkyl, C3-7 cycloalkyl, phenyl or naphthylwherein R₆ is unsubstituted or substituted by one or more R_(f); R_(f)is selected from the group consisting of C1-5 alkyl, C3-7 cycloalkyl,phenyl, naphthyl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl,tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl,isoquinolinyl, quinazolinyl and quinoxalinyl, C1-5 alkoxy, aryloxy,arylC1-5alkoxy, pyridylC1-5alkoxy, thienylC1-5alkoxy, furanylC1-5alkoxy,C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy,carbamoyl wherein the nitrogen atom is unsubstituted or independentlymono or di-substituted by C1-5 alkyl, aryl, heterocyclyl selected fromthe group consisting of piperidinyl, morpholinyl and piperazinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,quinolinyl and isoquinolinyl, C1-5 alkanoylamino, aroylamino, C1-5alkylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, arylthio wherein the sulfur atom is unoxidized oroxidized to a sulfoxide or sulfone, arylC1-5 alkylthio wherein thesulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, ureidowherein either nitrogen atom is unsubstituted or independentlysubstituted by C1-5 alkyl, aryl, heterocyclyl selected from the groupconsisting of piperidinyl, morpholinyl and piperazinyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyland isoquinolinyl, C1-5 alkoxycarbonylamino, aryloxycarbonylamino, C1-5alkylcarbamoyloxy, arylcarbamoyloxy, C1-5 alkylsulfonylamino,arylsulfonylamino, C1-5 alkylaminosulfonyl, arylaminosulfonyl, aminowherein the nitrogen atom is unsubstituted or independently mono ordi-substituted by C1-5 alkyl, aryl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl and piperazinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,quinolinyl and isoquinolinyl, halogen, hydroxy, oxo, carboxy and cyano,R_(f) is unsubstituted or substituted by one or more R_(g); R_(g) isselected from the group consisting of C1-5 alkyl, C3-7 cycloalkyl,phenyl unsubstituted or substituted by halogen, methyl or methoxy;naphthyl unsubstituted or substituted by halogen, methyl or methoxy;heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl;heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl,pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, C1-5 alkoxy, aryloxy, arylC1-5alkoxy,C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy,carbamoyl wherein the nitrogen atom is unsubstituted or independentlymono or di-substituted by C1-5 alkyl, aryl, heterocyclyl selected fromthe group consisting of piperidinyl, morpholinyl and piperazinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,quinolinyl and isoquinolinyl, C1-5 alkanoylamino, aroylamino, C1-5alkylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, arylthio wherein the sulfur atom is unoxidized oroxidized to a sulfoxide or sulfone, ureido wherein either nitrogen atomis unsubstituted or independently substituted by C1-5 alkyl, aryl,heterocyclyl selected from the group consisting of piperidinyl,morpholinyl and piperazinyl or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl andisoquinolinyl, C1-5 alkoxycarbonylamino, aryloxycarbonylamino, C1-5alkylcarbamoyloxy, arylcarbamoyloxy, C1-5 alkylsulfonylamino,arylsulfonylamino, C1-5 alkylaminosulfonyl, arylaminosulfonyl, aminowherein the nitrogen atom is unsubstituted or independently mono ordi-substituted by C1-5 alkyl, aryl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl and piperazinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,quinolinyl and isoquinolinyl, halogen, hydroxy, oxo, carboxy and cyano;R_(h) is selected from the group consisting of C1-5 alkyl, phenyl,naphthyl, C1-5 alkoxycarbonyl, aryloxycarbonyl, arylC1-3alkoxycarbonyl,carbamoyl wherein the nitrogen atom is unsubstituted or mono ordi-substituted by C1-5 alkyl, C3-6 cycloalkyl, phenyl, naphthyl,arylC1-3alkyl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl and piperazinyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyland isoquinolinyl, halogen, hydroxy, carboxy and cyano; Z is O or S;R_(j) is selected from the group consisting of C1-5alkyl,C3-6cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of piperidinyl, morpholinyl and piperazinyl; heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, tetrazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,quinolinyl and isoquinolinyl, arylC1-5alkyl, C1-5alkoxy, aryloxy,arylC1-5alkoxy, C1-5alkoxycarbonyl, aryloxycarbonyl, C1-5alkanoyloxy,aroyloxy, carbamoyl wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by C1-5alkyl, aryl, heterocyclylselected from the group consisting of piperidinyl, morpholinyl andpiperazinyl or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, tetrazolyl,pyridinyl, indolyl, benzofuranyl, benzothienyl, benzimidazolyl,benzthiazolyl, benzoxazolyl, quinolinyl and isoquinolinyl,C1-5alkanoylamino, aroylamino, C1-5alkylthio wherein the sulfur atom isunoxidized or oxidized to a sulfoxide or sulfone, arylthio wherein thesulfur atom is unoxidized or oxidized to a sulfoxide or sulfone,arylC1-5alkylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, ureido wherein either nitrogen atom isunsubstituted or independently substituted by C1-5 alkyl, aryl,heterocyclyl selected from the group consisting of piperidinyl,morpholinyl and piperazinyl or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, tetrazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl andisoquinolinyl, C1-5alkoxycarbonylamino, aryloxycarbonylamino, C1-5alkylcarbamoyloxy, arylcarbamoyloxy, C1-5alkylsulfonylamino,arylsulfonylamino, C1-5alkylaminosulfonyl, arylaminosulfonyl, aminowherein the nitrogen atom is unsubstituted or independently mono ordi-substituted by C1-5 alkyl, aryl, heterocyclyl selected from the groupconsisting of piperidinyl, morpholinyl and piperazinyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, tetrazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl and isoquinolinyl, halogen, hydroxy, oxo, carboxy,cyano, nitro, amidino and guanidino, R_(j) is unsubstituted orsubstituted by one or more R_(k); R_(k) is selected from the groupconsisting of C1-3 alkyl, C3-6 cycloalkyl, phenyl, naphthyl,heterocyclyl selected from the group consisting of piperidinyl,morpholinyl and piperazinyl; heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, tetrazolyl and pyridinyl, C1-3alkoxy, aryloxy, arylC1-3alkoxy, C1-3alkoxycarbonyl, aryloxycarbonyl,C1-3alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom isunsubstituted or independently mono or di-substituted by C1-3 alkyl,aryl, heterocyclyl selected from the group consisting of morpholinyl andpiperazinyl or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, tetrazolyl, andpyridinyl, C1-3alkanoylamino, aroylamino, C1-3alkylthio wherein thesulfur atom is unoxidized or oxidized to a sulfoxide or sulfone,arylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, ureido wherein either nitrogen atom isunsubstituted or independently substituted by C1-3alkyl, phenyl,naphthyl or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, tetrazolyl andpyridinyl, C1-3alkoxycarbonylamino, aryloxycarbonylamino,arylC1-3alkoxycarbonylamino, benzyloxycarbonylaminoC1-5 alkyl, C1-3alkylcarbamoyloxy, arylcarbamoyloxy, C1-3alkylsulfonylamino,arylsulfonylamino, C1-3alkylaminosulfonyl, arylaminosulfonyl, aminowherein the nitrogen atom is unsubstituted or independently mono ordi-substituted by C1-3alkyl, aryl, heterocyclyl selected from the groupconsisting of piperidinyl, morpholinyl and piperazinyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, tetrazolylpyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazoyl, benzthiazolyl, benzoxazolyl,quinolinyl and isoquinolinyl, halogen, hydroxy, oxo, carboxy, cyano andnitro; and X is O.
 5. The compound according to claim 4 wherein: R₁ ispiperidinyl, piperazinyl, furanyl, thienyl, pyrrolyl, oxazolyl,thiazolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl orisoquinolinyl, wherein R₁ is unsubstituted or substituted by one or moreR_(b); R_(b) is selected from the group consisting of C1-3 alkyl, C3-6cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl and piperazinyl,heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, tetrazolyl, pyridinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, quinolinyl and isoquinolinyl, C1-3 alkoxy, phenoxy, C1-3alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoylwherein the nitrogen atom is unsubstituted or independently mono ordi-substituted by C1-5 alkyl, phenyl or heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl andisoquinolinyl, C1-5 alkanoylamino, aroylamino, C1-5 alkylthio whereinthe sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone,arylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, ureido wherein either nitrogen atom isunsubstituted or independently substituted by C1-5alkyl, phenyl ornaphthyl; C1-5 alkoxycarbonylamino, C1-5 alkylcarbamoyloxy,arylcarbamoyloxy, C1-5 alkylsulfonylamino, arylsulfonylamino, C1-5alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atomis unsubstituted or independently mono or di-substituted by C1-5alkyl,phenyl, naphthyl, heterocyclyl selected from the group consisting ofpiperidinyl, morpholinyl and piperazinyl or heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl andisoquinolinyl, halogen, hydroxy, oxo, carboxy and cyano, R_(b) isunsubstituted or substituted by one or more R_(c); R_(c) is selectedfrom the group consisting of C1-3 alkyl, C5-6 cycloalkyl, aryl, C1-3alkoxy, phenoxy, halogen, hydroxy, oxo, carboxy and cyano; R₂ is H; R₃is C1-5 alkyl, C3-6 cycloalkyl or phenyl, wherein R₃ is unsubstituted orsubstituted by one or more R_(d); R_(d) is selected from the groupconsisting of C1-3 alkyl, C3-6 cycloalkyl, phenyl, naphthyl,heterocyclyl selected from the group consisting of piperidinyl,morpholinyl and piperazinyl; heteroaryl selected from the groupconsisting of furanyl, thienyl, thiazolyl, imidazolyl, pyridinyl,indolyl, quinolinyl and isoquinolinyl, C1-5 alkoxy, phenoxy, aroyl, C1-5alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoylwherein the nitrogen atom is unsubstituted or independently mono ordi-substituted by C1-5 alkyl, phenyl, naphthyl, heterocyclyl selectedfrom the group consisting of piperidinyl, morpholinyl and piperazinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl and indolyl, C1-5alkanoylamino, aroylamino, C1-3 alkylthio wherein the sulfur atom isunoxidized or oxidized to a sulfoxide or sulfone, phenylthio wherein thesulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, ureidowherein either nitrogen atom is unsubstituted or independentlysubstituted by C1-3 alkyl, phenyl or heteroaryl selected the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl and indolyl, C1-5 alkoxycarbonylamino, C1-5alkylcarbamoyloxy, arylcarbamoyloxy, C1-5 alkylsulfonylamino,arylsulfonylamino, amino wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by C1-3 alkyl, phenyl, heterocyclylselected from the group consisting of piperidinyl, morpholinyl andpiperazinyl or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl andindolyl, halogen, hydroxy, oxo, carboxy and cyano, R_(d) isunsubstituted or substituted by one or more R_(e); R_(e) is selectedfrom the group consisting of C1-5 alkyl, C5-6 cycloalkyl, phenyl,naphthyl, arylC1-3alkyl, C1-5 alkoxy, phenoxy, arylC1-3alkoxy, aroyl,amino, halogen, hydroxy, oxo, carboxy and cyano; wherein theconfiguration at the stereocenter defined by R₂ and R₃ and the carbonthey are attached to is L enantiomer; R₄ is H; R₅ is H or C1-3 alkyl; R₆is H, C1-5 alkyl, C3-6 cycloalkyl or phenyl. wherein R₆ is unsubstitutedor substituted by one or more R_(f); R_(f) is selected from the groupconsisting of C1-3 alkyl, C3-6 cycloalkyl, phenyl, naphthyl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl and piperazinyl; heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl andisoquinolinyl, C1-5 alkoxy, aryloxy, arylC1-3alkoxy, pyridylC1-5alkoxy,thienylC1-5alkoxy, furanylC1-5alkoxy, C1-5 alkoxycarbonyl,aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom is unsubstituted or independently mono or di-substitutedby C1-5 alkyl, phenyl or heteroaryl selected from the group consistingof furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl,pyridinyl and indolyl, C1-5 alkanoylamino, aroylamino, C1-3 alkylthiowherein the sulfur atom is unoxidized or oxidized to a sulfoxide orsulfone, arylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, arylC1-3 alkylthio wherein the sulfur atom isunoxidized or oxidized to a sulfoxide or sulfone, ureido wherein eithernitrogen atom is unsubstituted or independently substituted by C1-5alkyl or phenyl; C1-5 alkoxycarbonylamino, C1-5 alkylsulfonylamino,arylsulfonylamino, amino wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by C1-5 alkyl, phenyl, naphthyl,heterocyclyl selected from the group consisting of piperidinyl,morpholinyl and piperazinyl or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl and indolyl, halogen, hydroxy, oxo, carboxy andcyano, R_(f) is unsubstituted or substituted by one or more R_(g); R_(g)is selected from the group consisting of C1-3 alkyl, C5-6 cycloalkyl,phenyl unsubstituted or substituted by halogen, methyl or methoxy;heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl and piperazinyl; heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, pyrimidinyl, pyrazinyl and indolyl, C1-5 alkoxy,aryloxy, arylC1-3alkoxy, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom isunsubstituted or independently mono or di-substituted by C1-5 alkyl oraryl; C1-5 alkanoylamino, aroylamino, C1-5 alkylthio wherein the sulfuratom is unoxidized or oxidized to a sulfoxide or sulfone, arylthiowherein the sulfur atom is unoxidized or oxidized to a sulfoxide orsulfone, ureido wherein either nitrogen atom is unsubstituted orindependently substituted by C1-5 alkyl or aryl; C1-5alkoxycarbonylamino, aryloxycarbonylamino, C1-5 alkylcarbamoyloxy,arylcarbamoyloxy, C1-5 alkylsulfonylamino, arylsulfonylamino, C1-5alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atomis unsubstituted or independently mono or di-substituted by C1-5 alkylor aryl; halogen, hydroxy, oxo, carboxy and cyano; R_(h) is selectedfrom the group consisting of C1-5 alkyl, phenyl, C1-5 alkoxycarbonyl,aryloxycarbonyl, arylC1-3alkoxycarbonyl, carbamoyl wherein the nitrogenatom is unsubstituted or mono or di-substituted by C1-5 alkyl, C3-6cycloalkyl, phenyl or naphthyl, arylC1-3alkyl, halogen, hydroxy, carboxyand cyano; Z is O; R₈ is a heteroaryl ring selected from the groupconsisting of oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl,isothiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,quinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl, wherein any ofthe above R₈ can be unsubstituted or substituted by one or more R_(j);R_(j) is selected from the group consisting of C1-3 alkyl, C5-6cycloalkyl, phenyl, naphthyl, morpholinyl, piperazinyl, furanyl,thienyl, pyrrolyl, tetrazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,arylC1-3alkyl, C1-3alkoxy, aryloxy, arylC1-3alkoxy, C1-3alkoxycarbonyl,aryloxycarbonyl, C1-3alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom is unsubstituted or independently mono or di-substitutedby C1-3alkyl, phenyl, naphthyl, piperidinyl, furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, tetrazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,quinolinyl or isoquinolinyl; C1-3alkanoylamino, aroylamino,C1-3alkylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, arylthio wherein the sulfur atom is unoxidized oroxidized to a sulfoxide or sulfone, arylC1-3alkylthio wherein the sulfuratom is unoxidized or oxidized to a sulfoxide or sulfone, ureido whereineither nitrogen atom is unsubstituted or independently substituted byC1-3 alkyl, phenyl, naphthyl, piperidinyl, morpholinyl, thiazolyl,imidazolyl, tetrazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl orisoquinolinyl; C1-3 alkoxycarbonylamino, aryloxycarbonylamino, C1-3alkylcarbamoyloxy, arylcarbamoyloxy, C1-3 alkylsulfonylamino,arylsulfonylamino, C1-3 alkylaminosulfonyl, arylaminosulfonyl, aminowherein the nitrogen atom is unsubstituted or independently mono ordi-substituted by C1-3 alkyl, phenyl, naphthyl, piperidinyl, furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, tetrazolyl,pyridinyl, indolyl, benzofuranyl, benzothienyl, benzimidazolyl,benzthiazolyl, benzoxazolyl, quinolinyl or isoquinolinyl; halogen,hydroxy, oxo, carboxy, cyano and nitro, R_(j) is unsubstituted orsubstituted by one or more R_(k); R_(k) is selected from the groupconsisting of methyl, C5-6 cycloalkyl, phenyl, morpholinyl, furanyl,thienyl, pyrrolyl, tetrazolyl, pyridinyl, methoxy, phenoxy, benzyloxy,methoxycarbonyl, acetyloxy, benzoyloxy, carbamoyl wherein the nitrogenatom is unsubstituted or independently mono or di-substituted by C1-3alkyl, phenyl, furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl or pyridinyl; acetylamino, benzoylamino, methylthio whereinthe sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone,ureido wherein either nitrogen atom is unsubstituted or independentlysubstituted by methyl, phenyl, furanyl, thienyl, pyrrolyl, oxazolyl,thiazolyl, imidazolyl or pyridinyl; arylC1-3alkoxycarbonylamino,benzyloxycarbonylaminoC1-5alkyl, amino wherein the nitrogen atom isunsubstituted or independently mono or di-substituted by C1-3alkyl,phenyl, naphthyl, furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl orisoquinolinyl, halogen, hydroxy, oxo, carboxy, cyano and nitro.
 6. Thecompound according to claim 5 wherein: R₁ is piperidinyl, piperazinyl,furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinylor indolyl, wherein R₁ is unsubstituted or substituted by one or moreR_(b); R_(b) is selected from the group consisting of C1-3 alkyl, C5-6cycloalkyl, phenyl, heterocyclyl selected from the group consisting ofpiperidinyl, morpholinyl and piperazinyl; heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, imidazolyl, tetrazolyl,pyridinyl, indolyl, benzofuranyl, benzothienyl, benzimidazolyl,benzthiazolyl, benzoxazolyl, quinolinyl and isoquinolinyl, C1-3 alkoxy,C1-3 alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy,carbamoyl wherein the nitrogen atom is unsubstituted or independentlymono or di-substituted by C1-3 alkyl, phenyl or heteroaryl selected fromthe group consisting of pyrrolyl, imidazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl and benzthiazolyl; C1-5alkanoylamino, aroylamino, C1-3 alkylthio wherein the sulfur atom isunoxidized or oxidized to a sulfoxide or sulfone, arylthio wherein thesulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, ureidowherein either nitrogen atom is unsubstituted or independentlysubstituted by C1-3alkyl or phenyl; C1-5 alkylsulfonylamino,arylsulfonylamino, amino wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by C1-3alkyl, phenyl, heterocyclylselected from the group consisting of piperidinyl, morpholinyl andpiperazinyl or heteroaryl selected from the group consisting ofpyrrolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl andisoquinolinyl; halogen, hydroxy, oxo, carboxy and cyano, R_(b) isunsubstituted or substituted by one or more R_(c); R_(c) is selectedfrom the group consisting of C1-3 alkyl, C5-6 cycloalkyl, C1-3 alkoxy,halogen and hydroxy; R₃ is C1-5 alkyl, C5-6 cycloalkyl or phenyl whereinR₃ is unsubstituted or substituted by one or more R_(d); R_(d) isselected from the group consisting of C1-3 alkyl, C3-6 cycloalkyl,phenyl, naphthyl, 4-piperidinyl, 4-morpholinyl, piperazinyl, furanyl,thienyl, thiazolyl, imidazolyl, pyridinyl, indolyl, C1-5 alkoxy,phenoxy, aroyl, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy,aroyloxy, carbamoyl wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by C1-5 alkyl or phenyl; C1-5alkanoylamino, C1-3 alkylthio wherein the sulfur atom is unoxidized oroxidized to a sulfoxide or sulfone, ureido wherein either nitrogen atomis unsubstituted or independently substituted by C1-3 alkyl or phenyl;C1-5 alkoxycarbonylamino, C1-5 alkylsulfonylamino, arylsulfonylamino,amino wherein the nitrogen atom is unsubstituted or independently monoor di-substituted by C1-3 alkyl or phenyl; halogen, hydroxy, oxo,carboxy and cyano, R_(d) is unsubstituted or substituted by one or moreR_(e); R_(e) is selected from the group consisting of C1-5 alkyl, C5-6cycloalkyl, phenyl, benzyl, C1-5 alkoxy, phenoxy, benzyloxy, aroyl,halogen, hydroxy, oxo, carboxy and cyano; R₆ is H, C1-5 alkyl or phenylwherein R₆ is unsubstituted or substituted by one or more R_(f); R_(f)is selected from the group consisting of C1-3 alkyl, C3-6 cycloalkyl,phenyl, naphthyl, furanyl, thienyl, thiazolyl, imidazolyl, pyridinyl,indolyl, C1-3 alkoxy, benzyloxy, pyridyl, C1-3alkoxy, thienylC1-3alkoxy,furanylC1-3alkoxy, C1-3 alkoxycarbonyl, phenoxyoxycarbonyl, C1-5alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom isunsubstituted or independently mono or di-substituted by C1-3 alkyl orphenyl; C1-5 alkanoylamino, aroylamino, methylthio wherein the sulfuratom is unoxidized or oxidized to a sulfoxide or sulfone, benzylthiowherein the sulfur atom is unoxidized or oxidized to a sulfoxide orsulfone, ureido wherein either nitrogen atom is unsubstituted orindependently substituted by C1-5 alkyl or phenyl; C1-3alkoxycarbonylamino, amino wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by C1-5 alkyl or phenyl; halogen,hydroxy, oxo, carboxy and cyano, R_(f) is unsubstituted or substitutedby one or more R_(g); R_(g) is selected from the group consisting ofC1-3 alkyl, phenyl unsubstituted or substituted by halogen, methyl ormethoxy; heterocyclyl selected from the group consisting of piperidinyl,morpholinyl and piperazinyl; heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl and pyridinyl, C1-3 alkoxy,aryloxy, benzyloxy, C1-5 alkoxycarbonyl, C1-5 alkanoyloxy, aroyloxy,carbamoyl wherein the nitrogen atom is unsubstituted or independentlymono or di-substituted by C1-5 alkyl or phenyl; C1-5 alkanoylamino,aroylamino, C1-5 alkylthio wherein the sulfur atom is unoxidized oroxidized to a sulfoxide or sulfone, ureido wherein either nitrogen atomis unsubstituted or independently substituted by C1-5 alkyl or phenyl;C1-5 alkoxycarbonylamino, C1-5 alkylcarbamoyloxy, arylcarbamoyloxy, C1-3alkylsulfonylamino, arylsulfonylamino, C1-3 alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by C1-3 alkyl or phenyl; halogen,hydroxy, oxo, carboxy and cyano; R_(h) is selected from the groupconsisting of C1-3 alkyl, phenyl, C1-3 alkoxycarbonyl,phenoxyoxycarbonyl, benzyloxy, carbamoyl wherein the nitrogen atom isunsubstituted or mono or di-substituted with C1-5 alkyl, phenyl, benzyl,halogen, hydroxy, carboxy and cyano; R₈ is a heteroaryl ring selectedfrom the group consisting of oxazolyl, thiazolyl, imidazolyl, pyridyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, quinolinyl and isoquinolinyl, wherein any of the above R₈can be unsubstituted or substituted by one or more R_(j); R_(j) isselected from the group consisting of C1-3 alkyl, C5-6 cycloalkyl,phenyl, naphthyl, morpholinyl, piperazinyl, furanyl, thienyl, pyrrolyl,tetrazolyl, pyridinyl, benzyl, C1-3alkoxy, phenoxy, benzyloxy,C1-3alkoxycarbonyl, acetyloxy, benzoyloxy, carbamoyl wherein thenitrogen atom is unsubstituted or independently mono or di-substitutedby methyl, phenyl, furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl or pyridinyl; acetylamino, benzoylamino, methylthio whereinthe sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone,benzylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, ureido wherein either nitrogen atom isunsubstituted or independently substituted by methyl, phenyl, thiazolyl,imidazolyl or pyridinyl; C1-3 alkoxycarbonylamino, C1-3alkylcarbamoyloxy, arylcarbamoyloxy, C1-3alkylsulfonylamino,arylsulfonylamino, amino wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by methyl, phenyl, furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl or pyridinyl;halogen, hydroxy, carboxy, cyano and nitro, R_(j) is unsubstituted orsubstituted by one or more R_(k); R_(k) is selected from the groupconsisting of methyl, C5-6 cycloalkyl, phenyl, furanyl, thienyl,pyrrolyl, pyridinyl, methoxy, phenoxy, benzyloxy, methoxycarbonyl,acetyloxy, benzoyloxy, carbamoyl wherein the nitrogen atom isunsubstituted or independently mono or di-substituted by methyl, phenyl,furanyl or thienyl; acetylamino, benzoylamino, methylthio wherein thesulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, ureidowherein either nitrogen atom is unsubstituted or independentlysubstituted by methyl, phenyl, furanyl, thienyl, pyrrolyl, oxazolyl andthiazolyl, benzyloxycarbonylamino, benzyloxycarbonylaminoC1-5alkyl,amino wherein the nitrogen atom is unsubstituted or independently monoor di-substituted by C1-3alkyl, phenyl, furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl and pyridinyl, halogen, hydroxy,carboxy, cyano and nitro.
 7. The compound according to claim 6 wherein:R₁ is piperidinyl, piperazinyl, furanyl, thienyl or pyrrolyl, wherein R₁is unsubstituted or substituted by one or more R_(b); R_(b) is selectedfrom the group consisting of C1-3 alkyl, C5-6 cycloalkyl, phenyl,furanyl, thienyl, pyrrolyl, imidazolyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, C1-3 alkoxy,C1-3 alkoxycarbonyl, carbamoyl wherein the nitrogen atom isunsubstituted or independently mono or di-substituted by C1-3 alkyl orphenyl; C1-5 alkanoylamino, aroylamino, ureido wherein either nitrogenatom is unsubstituted or independently substituted by C1-3alkyl orphenyl; C1-5 alkylsulfonylamino, arylsulfonylamino, amino wherein thenitrogen atom is unsubstituted or independently mono or di-substitutedby C1-3alkyl or phenyl; halogen, hydroxy, oxo, carboxy and cyano, R_(b)is unsubstituted or substituted by one or more R_(c); R_(c) is selectedfrom the group consisting of C1-3 alkyl, C1-3 alkoxy, halogen andhydroxy; R_(d) is selected from the group consisting of C1-3 alkyl, C3-6cycloalkyl, phenyl, naphthyl, 4-piperidinyl, furanyl, thienyl,thiazolyl, imidazolyl, pyridinyl, indolyl, C1-3alkoxy,C1-5alkoxycarbonyl, C1-5alkanoyloxy, benzoyloxy, carbamoyl wherein thenitrogen atom is unsubstituted or independently mono or di-substitutedby C1-3alkyl or phenyl; C1-5alkanoylamino, C1-3 alkylthio wherein thesulfur atom is unoxidized or oxidized to a sulfoxide or sulfone,C1-3alkoxycarbonylamino, C1-3alkylsulfonylamino, amino wherein thenitrogen atom is unsubstituted or independently mono or di-substitutedby C1-3 alkyl or phenyl, halogen, hydroxy, oxo, carboxy and cyano, R_(d)is unsubstituted or substituted by one or more R_(e); R_(e) is selectedfrom the group consisting of C1-3 alkyl, phenyl, benzyl, C1-3 alkoxy,phenoxy, benzyloxy, benzoyl, halogen, hydroxy, oxo, carboxy and cyano;R₅ is H or methyl; R₆ is C1-5 alkyl or phenyl, wherein R₆ isunsubstituted or substituted by one or more groups of the formula R_(f),R_(f) is selected from the group consisting of methyl, C3-6 cycloalkyl,phenyl, naphthyl, furanyl, thienyl, thiazolyl, imidazolyl, pyridinyl,indolyl, C1-3 alkoxy, benzyloxy, C1-5 alkanoylamino, aroylamino,methylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, benzylthio wherein the sulfur atom is unoxidizedor oxidized to a sulfoxide or sulfone, C1-3 alkoxycarbonylamino, aminowherein the nitrogen atom is unsubstituted or independently mono ordi-substituted by C1-5 alkyl or phenyl; halogen, hydroxy, oxo, carboxyand cyano, R_(f) is unsubstituted or substituted by one or more R_(g);R_(g) is selected from the group consisting of C1-3 alkyl, phenylunsubstituted or substituted by halogen or methyl; C1-3 alkoxy, aryloxy,benzyloxy, C1-3 alkoxycarbonyl, carbamoyl wherein the nitrogen atom isunsubstituted or independently mono or di-substituted by C1-3 alkyl orphenyl; C1-5 alkanoylamino, aroylamino, amino wherein the nitrogen atomis unsubstituted or independently mono or di-substituted by C1-3 alkylor phenyl; halogen, hydroxy, oxo, carboxy and cyano; R_(h) is selectedfrom the group consisting of C1-3 alkyl, phenyl, C1-3 alkoxycarbonyl,benzyloxy and carboxy; R₈ is a heteroaryl ring selected from the groupconsisting of oxazolyl, thiazolyl, imidazolyl, pyridyl, benzimidazolyl,benzthiazolyl and benzoxazolyl, wherein any of the above R₈ can beunsubstituted or substituted by one or more R_(j); R_(j) is selectedfrom the group consisting of methyl, cyclohexyl, phenyl, furanyl,thienyl, benzyl, methoxy, phenoxy, benzyloxy, methoxycarbonyl,acetyloxy, benzoyloxy, carbamoyl wherein the nitrogen atom isunsubstituted or independently mono or di-substituted by methyl, phenyl,furanyl or thienyl; acetylamino, benzoylamino, ureido wherein eithernitrogen atom is unsubstituted or independently substituted by methyl orphenyl; methoxycarbonylamino, C1-3 alkylsulfonylamino,arylsulfonylamino, amino wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by methyl, phenyl, furanyl orthienyl; halogen, hydroxy, carboxy and cyano, R_(j) is unsubstituted orsubstituted by one or more R_(k); R_(k) is selected from the groupconsisting of methyl, phenyl, furanyl, thienyl, methoxy, phenoxy,benzyloxy, methoxycarbonyl, acetyloxy, benzoyloxy, carbamoyl wherein thenitrogen atom is unsubstituted or independently mono or di-substitutedby methyl or phenyl; acetylamino, benzoylamino, ureido wherein eithernitrogen atom is unsubstituted or independently substituted by methyl orphenyl; benzyloxycarbonylamino, benzyloxycarbonylaminoC1-3alkyl, aminowherein the nitrogen atom is unsubstituted or independently mono ordi-substituted by C1-3alkyl, phenyl, furanyl or thienyl; halogen,hydroxy, carboxy, cyano and nitro.
 8. The compound according to claim 7wherein: A is —C(O)— or —SO₂—; R₁ is piperidinyl or piperazinyl, whereinR1 is unsubstituted or substituted by one or more R_(b); R_(b) isselected from the group consisting of C1-3 alkyl, C5-6 cycloalkyl,phenyl, furanyl, thienyl, pyrrolyl, imidazolyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, C1-3 alkoxy,C1-3 alkoxycarbonyl, carbamoyl wherein the nitrogen atom isunsubstituted or independently mono or di-substituted by C1-3 alkyl orphenyl; C1-5 alkanoylamino, aroylamino, C1-5 alkylsulfonylamino,arylsulfonylamino, amino wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by C1-3 alkyl; halogen, hydroxy,oxo, carboxy and cyano, R_(b) is unsubstituted or substituted by one ormore R_(c); R_(c) is selected from the group consisting of C1-3 alkoxy,halogen and hydroxy; R₃ is C1-5 alkyl or C5-6 cycloalkyl, wherein R₃ isunsubstituted or substituted by one or more R_(d); R_(d) is selectedfrom the group consisting of methyl, C3-6 cycloalkyl, phenyl, thienyl,imidazolyl, pyridinyl, indolyl, C1-4 alkoxy, C1-5 alkanoylamino,methylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, halogen, hydroxy, oxo, carboxy and cyano, R_(d) isunsubstituted or substituted by one or more R_(e); R_(e) is selectedfrom the group consisting of methyl, phenyl, benzyl, methoxy, phenoxy,benzyloxy, benzoyl, halogen and hydroxy; R_(f) is selected from thegroup consisting of C3-6 cycloalkyl, phenyl, naphthyl, thienyl,imidazolyl, pyridinyl, indolyl, methoxy, benzyloxy, C1-3 alkanoylamino,methylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, benzylthio wherein the sulfur atom is unoxidizedor oxidized to a sulfoxide or sulfone, methoxycarbonylamino, aminowherein the nitrogen atom is unsubstituted or independently mono ordi-substituted by C1-3 alkyl; halogen, hydroxy, carboxy and cyano, R_(f)is unsubstituted or substituted by one or more R_(g); R_(g) is selectedfrom the group consisting of methyl, phenyl unsubstituted or substitutedby halogen or methyl; methoxy, phenoxy, benzyloxy, methoxycarbonyl,amino wherein the nitrogen atom is unsubstituted or independently monoor di-substituted by C1-3 alkyl or phenyl; halogen, hydroxy and carboxy;R₈ is a heteroaryl ring selected from the group consisting of oxazolyl,thiazolyl, imidazolyl, pyridyl, benzthiazolyl and benzoxazolyl, whereinany of the above R₈ can be unsubstituted or substituted by one or moreR_(j); R_(j) is selected from the group consisting of methyl, phenyl,furanyl, thienyl, benzyl, methoxy, methoxycarbonyl, acetyloxy,benzoyloxy, carbamoyl wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by methyl or phenyl; acetylamino,benzoylamino, ureido wherein either nitrogen atom is unsubstituted orindependently substituted by methyl or phenyl; methoxycarbonylamino,amino wherein the nitrogen atom is unsubstituted or independently monoor di-substituted by methyl or phenyl; halogen, hydroxy, carboxy andcyano, R_(j) is unsubstituted or substituted by one or more R_(k); R_(k)is selected from the group consisting of methyl, phenyl, methoxy,phenoxy, benzyloxy, methoxycarbonyl, carbamoyl wherein the nitrogen atomis unsubstituted or independently mono or di-substituted by methyl orphenyl; ureido wherein either nitrogen atom is unsubstituted orindependently substituted by methyl or phenyl; benzyloxycarbonylamino,benzyloxycarbonylaminoC1-5alkyl, amino wherein the nitrogen atom isunsubstituted or independently mono or di-substituted by C1-3alkyl,phenyl, furanyl or thienyl; halogen, hydroxy, carboxy, cyano and nitro.9. The compound according to claim 8 wherein: R_(b) is selected from thegroup consisting of, pyrrolyl, imidazolyl, indolyl, benzimidazolyl,methoxy, methoxycarbonyl, amino wherein the nitrogen atom isunsubstituted or independently mono or di-substituted by C1-3 alkyl;halogen, hydroxy and carboxy, R_(b) is unsubstituted or substituted byone or more R_(c); R_(c) is selected from the group consisting ofmethoxy, halogen and hydroxy; R_(d) is selected from the groupconsisting of methyl, C3-6 cycloalkyl, phenyl, C1-4 alkoxy, C1-3alkanoylamino, methylthio wherein the sulfur atom is unoxidized oroxidized to a sulfoxide or sulfone, halogen, hydroxy, oxo, carboxy andcyano, R_(d) is unsubstituted or substituted by one or more R_(c); R_(c)is selected from the group consisting of methyl, phenyl, methoxy,halogen and hydroxy; R₅ is H; R_(f) is selected from the groupconsisting of C5-6 cycloalkyl, phenyl, naphthyl, thienyl, indolyl,methoxy, methylthio wherein the sulfur atom is unoxidized or oxidized toa sulfoxide or sulfone, methoxycarbonylamino, halogen, hydroxy, carboxyand cyano, R_(f) is unsubstituted or substituted by one or more R_(g);R_(g) is selected from the group consisting of methyl, phenylunsubstituted or substituted by halogen; methoxy, phenoxy, benzyloxy,methoxycarbonyl, halogen, hydroxy and carboxy; R₈ is a heteroaryl ringselected from the group consisting of oxazolyl, pyridyl, benzthiazolyland benzoxazolyl, wherein any of the above R₈ can be unsubstituted orsubstituted by one or more R_(j); R_(j) is selected from the groupconsisting of methyl, phenyl, benzyl, methoxy, methoxycarbonyl,acetyloxy, benzoyloxy, carbamoyl wherein the nitrogen atom isunsubstituted or independently mono or di-substituted by methyl orphenyl; methoxycarbonylamino, halogen, hydroxy and carboxy, R_(j) isunsubstituted or substituted by one or more R_(k); R_(k) is selectedfrom the group consisting of methyl, phenyl, methoxy, methoxycarbonyl,carbamoyl wherein the nitrogen atom is unsubstituted or independentlymono or di-substituted by methyl or phenyl; benzyloxycarbonylamino,amino wherein the nitrogen atom is unsubstituted or independently monoor di-substituted by methyl or phenyl; halogen, hydroxy and carboxy. 10.The compound according to claim 9 wherein: R_(b) is selected from thegroup consisting of benzimidazolyl, methoxy and dimethylamino, R_(b) isunsubstituted or substituted by a halogen atom; R₃ is C1-5 alkyl whereinR₃ is unsubstituted or substituted by one or more R_(d); R_(d) isselected from the group consisting of C3-6 cycloalkyl and phenyl, R_(d)is unsubstituted or substituted by one or more R_(e); R_(e) is selectedfrom the group consisting of methyl and halogen; R₆ is C1-5 alkylunsubstituted or substituted by one or more R_(f); R_(f) is selectedfrom the group consisting of C5-6 cycloalkyl, phenyl, methylthio whereinthe sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, andhalogen, R_(f) is unsubstituted or substituted by one or more R_(g);R_(g) is selected from the group consisting of methyl, methoxy,methoxycarbonyl, halogen and hydroxy; R_(j) is selected from the groupconsisting of phenyl, methoxycarbonyl, carbamoyl wherein the nitrogenatom is unsubstituted or independently mono or disubstituted by methylor phenyl; methoxycarbonylamino and halogen, R_(j) is unsubstituted orsubstituted by one or more R_(k); R_(k) is selected from the groupconsisting of phenyl, methoxycarbonyl, carbamoyl, benzyloxycarbonylaminoand halogen.
 11. A compound of formula (Ia):

wherein: A is —C(Y)— or —SO₂— Y is O, S or NR_(a) wherein R_(a) isselected from the group consisting of H, alkyl, aryl, alkoxy, aryloxy,alkylamino and arylamino; R₁ is thiomorpholinyl, piperidinyl,pyrrolidinyl, piperazinyl, furanyl, thienyl, pyridinyl, pyridazinyl,pyrimidinyl, pyrazinyl, indolyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyl orphenoxazinyl wherein R₁ is unsubstituted or substituted by one or moreR_(b); R_(b) is selected from the group consisting of alkyl, cycloalkyl,aryl, heterocyclyl, heteroaryl, alkoxy, aryloxy, alkoxycarbonyl,aryloxycarbonyl, alkanoyl, aroyl, alkanoyloxy, aroyloxy, carbamoylwherein the nitrogen atom is unsubstituted or independently mono ordi-substituted by alkyl, aryl, heterocyclyl or heteroaryl,alkanoylamino, aroylamino, alkylthio wherein the sulfur atom isunoxidized or oxidized to a sulfoxide or sulfone, arylthio wherein thesulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, ureidowherein either nitrogen atom is unsubstituted or independentlysubstituted by alkyl, aryl, heterocyclyl or heteroaryl,alkoxycarbonylamino, aryloxycarbonylamino, alkylcarbamoyloxy,arylcarbamoyloxy, alkylsulfonylamino, arylsulfonylamino,alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atomis unsubstituted or independently mono or di-substituted by alkyl, aryl,heterocyclyl or heteroaryl, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino, R_(b) is unsubstituted or substituted byone or more R_(c); R_(c) is selected from the group consisting of alkyl,cycloalkyl, aryl, heterocycle, heteroaryl, arylalkyl, alkoxy, aryloxy,arylalkoxy, alkanoyl, aroyl, amino wherein the nitrogen atom isunsubstituted or independently mono or di-substituted by alkyl, aryl,heterocyclyl or heteroaryl, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino; R₂ is H or alkyl; R₃ is H, alkyl,cycloalkyl, aryl, heterocyclyl or heteroaryl, wherein R₃ isunsubstituted or substituted by one or more groups of the formula R_(d);R_(d) is selected from the group consisting of alkyl, cycloalkyl, aryl,heterocyclyl, heteroaryl, alkoxy, aryloxy, arylalkoxy, alkoxycarbonyl,aryloxycarbonyl, alkanoyl, aroyl, alkanoyloxy, aroyloxy, carbamoylwherein the nitrogen atom is unsubstituted or independently mono ordi-substituted by alkyl, aryl, heterocyclyl or heteroaryl,alkanoylamino, aroylamino, alkylthio wherein the sulfur atom isunoxidized or oxidized to a sulfoxide or sulfone, arylthio wherein thesulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, ureidowherein either nitrogen atom is unsubstituted or independentlysubstituted by alkyl, aryl, heterocyclyl or heteroaryl,alkoxycarbonylamino, aryloxycarbonylamino, alkylcarbamoyloxy,arylcarbamoyloxy, alkylsulfonylamino, arylsulfonylamino,alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atomis unsubstituted or independently mono or di-substituted by alkyl, aryl,heterocyclyl or heteroaryl, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino, R_(d) is unsubstituted or substituted byone or more R_(e); R_(e) is selected from the group consisting of alkyl,cycloalkyl, aryl, arylalkyl, alkoxy, aryloxy, arylalkoxy, alkanoyl,aroyl, amino, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino andguanidino; R₄ is H or alkyl; R₅ is H, alkyl or cycloalkyl; R₆ is H,alkyl, cycloalkyl, aryl, heterocyclyl or heteroaryl, wherein R₆ isunsubstituted or substituted by one or more groups of the formula R_(f);R_(f) is selected from the group consisting of alkyl, cycloalkyl, aryl,heterocyclyl, heteroaryl, alkoxy, aryloxy, alkanoyl, aroyl, arylalkoxy,heteroarylalkoxy, alkoxycarbonyl, aryloxycarbonyl, alkanoyloxy,aroyloxy, carbamoyl wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by alkyl, aryl, heterocyclyl orheteroaryl, alkanoylamino, aroylamino, alkylthio wherein the sulfur atomis unoxidized or oxidized to a sulfoxide or sulfone, arylthio whereinthe sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone,arylalkylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, ureido wherein either nitrogen atom isunsubstituted or independently substituted by alkyl, aryl, heterocyclylor heteroaryl, alkoxycarbonylamino, aryloxycarbonylamino,alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino,arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino whereinthe nitrogen atom is unsubstituted or independently mono ordi-substituted by alkyl, aryl, heterocyclyl or heteroaryl, halogen,hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino, R_(f) isunsubstituted or substituted by one or more R_(g); R_(g) is selectedfrom the group consisting of alkyl, cycloalkyl, aryl unsubstituted orsubstituted by halogen, C1-5alkyl or C1-5alkoxy, heterocyclyl,heteroaryl, alkoxy, aryloxy, arylalkoxy, alkoxycarbonyl,aryloxycarbonyl, alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogenatom is unsubstituted or independently mono or di-substituted by alkyl,aryl, heterocyclyl or heteroaryl; alkanoylamino, aroylamino, alkylthiowherein the sulfur atom is unoxidized or oxidized to a sulfoxide orsulfone, arylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, ureido wherein either nitrogen atom isunsubstituted or independently substituted by alkyl, aryl, heterocyclylor heteroaryl; alkoxycarbonylamino, aryloxycarbonylamino,alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino,arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino whereinthe nitrogen atom is unsubstituted or independently mono ordi-substituted by alkyl, aryl, heterocyclyl or heteroaryl; halogen,hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino; or R₅together with R₆ form a 3 to 6 membered carbocyclic ring, thecarbocyclic ring being unsubstituted or substituted with one or moreR_(h); R_(h) is selected from the group consisting of alkyl, aryl,alkoxycarbonyl, aryloxycarbonyl, arylalkoxycarbonyl, carbamoyl whereinthe nitrogen atom is unsubstituted or mono or di-substituted by alkyl,cycloalkyl, aryl, arylalkyl, heterocyclyl or heteroaryl; halogen,hydroxy, carboxy and cyano; R₇ is R8-C(Z)-; wherein Z is O, S, or NR_(i)wherein R_(i) is selected from the group consisting of H, alkyl, aryl,alkoxy, aryloxy and hydroxy; R₈ is a heteroaryl ring selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, pyridyl, pyridazinyl,pyrimidinyl, pyrazinyl, triazinyl, indolizinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, triazolyl, tetrazolyl, purinyl, quinolizinyl, quinolinyl,isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl,naphthyridinyl, pteridinyl, carbazolyl, acridinyl and phenazinyl,wherein any of the above R₈ can be unsubstituted or substituted by oneor more R_(j); R_(j) is selected from the group consisting of alkyl,cycloalkyl, aryl, heterocyclyl, heteroaryl, arylalkyl, alkoxy, aryloxy,alkanoyl, aroyl, arylalkoxy, alkoxycarbonyl, aryloxycarbonyl,alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom isunsubstituted or independently mono or di-substituted by alkyl, aryl,heterocyclyl or heteroaryl, alkanoylamino, aroylamino, alkylthio whereinthe sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone,arylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, arylalkylthio wherein the sulfur atom isunoxidized or oxidized to a sulfoxide or sulfone, ureido wherein eithernitrogen atom is unsubstituted or independently substituted by alkyl,aryl, heterocyclyl or heteroaryl; alkoxycarbonylamino,aryloxycarbonylamino, alkylcarbamoyloxy, arylcarbamoyloxy,alkylsulfonylamino, arylsulfonylamino, alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by alkyl, aryl, heterocyclyl orheteroaryl; halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino andguanidino, R_(j) is unsubstituted or substituted by one or more R_(k);R_(k) is selected from the group consisting of alkyl, cycloalkyl, aryl,heterocyclyl, heteroaryl, alkoxy, aryloxy, arylalkoxy, alkoxycarbonyl,aryloxycarbonyl, alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogenatom is unsubstituted or independently mono or di-substituted by alkyl,aryl, heterocyclyl or heteroaryl, alkanoylamino, aroylamino, alkylthiowherein the sulfur atom is unoxidized or oxidized to a sulfoxide orsulfone, arylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, ureido wherein either nitrogen atom isunsubstituted or independently substituted by alkyl, aryl, heterocyclylor heteroaryl, alkoxycarbonylamino, aryloxycarbonylamino,arylalkoxycarbonylamino, arylalkoxycarbonylaminoalkyl,alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino,arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino whereinthe nitrogen atom is unsubstituted or independently mono ordi-substituted by alkyl, aryl, heterocyclyl or heteroaryl, halogen,hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino, whereinR_(k) is unsubstituted or substituted by R1; R₁ is selected from thegroup consisting of alkyl, cycloalkyl, aryl, and benzyl; and X is O, Sor N—OH; or the pharmaceutically acceptable salts, esters, tautomers,individual isomers and mixtures of isomers thereof; with the followingprovisos: when R₆ is alkyl the alkyl must be substituted with R_(f)wherein R_(f) is not hydroxy, sulfhydryl or halogen; and when R₁ isC1alkyl then R_(b) cannot be carbamoyl, alkanoylamino, aroylamino,ureido, alkoxycarbonylamino, aryloxycarbonylamino, alkylsulfonylamino,arylsulfonylamino, amino, amidino or guanidino wherein each said R_(b)is linked to said R₁ via the nitrogen atom thereof.
 12. The compoundaccording to claim 11 wherein: R_(a) is selected from the groupconsisting of H, alkyl and aryl; R_(b) is selected from the groupconsisting of C1-8 alkyl, C3-7 cycloalkyl, aryl, heterocyclyl selectedfrom the group consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl; heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, C1-8 alkoxy, aryloxy, C1-8 alkoxycarbonyl,aryloxycarbonyl, C1-8 alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom is unsubstituted or independently mono or di-substitutedby C1-8 alkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl, or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, C1-8 alkanoylamino,aroylamino, C1-8 alkylthio wherein the sulfur atom is unoxidized oroxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom isunoxidized or oxidized to a sulfoxide or sulfone, ureido wherein eithernitrogen atom is unsubstituted or independently substituted by alkyl,aryl, heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl,oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyridinyl,pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl and phenoxazinyl, alkoxycarbonylamino,aryloxycarbonylamino, C1-8 alkylcarbamoyloxy, arylcarbamoyloxy,alkylsulfonylamino, arylsulfonylamino, alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl,triazolyl, tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl,pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidinoand guanidino, R_(b) is unsubstituted or substituted by one or moreR_(c); R_(c) is selected from the group consisting of C1-8 alkyl, C3-6cycloalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, C1-8 alkoxy, aryloxy,halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino; R₃is H, C1-8 alkyl, C3-7 cycloalkyl or aryl wherein R₃ is unsubstituted orsubstituted by one or more R_(d); R_(d) is selected from the groupconsisting of C1-8 alkyl, C3-7 cycloalkyl, aryl, heterocyclyl selectedfrom the group consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl; heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, C1-8 alkoxy, aryloxy, alkanoyl, aroyl, C1-8alkoxycarbonyl, aryloxycarbonyl, C1-8 alkanoyloxy, aroyloxy, carbamoylwherein the nitrogen atom is unsubstituted or independently mono ordi-substituted by C1-8 alkyl, aryl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl, or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, C1-8 alkanoylamino, aroylamino, C1-8 alkylthio whereinthe sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone,arylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, ureido wherein either nitrogen atom isunsubstituted or independently substituted by alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl,triazolyl, tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl,pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, alkoxycarbonylamino, aryloxycarbonylamino, C1-8alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino,arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino whereinthe nitrogen atom is unsubstituted or independently mono ordi-substituted by alkyl, aryl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidinoand guanidino, R_(d) is unsubstituted or substituted by one or moreR_(e); R_(e) is selected from the group consisting of C1-8 alkyl, C3-6cycloalkyl, aryl, arylalkyl, C1-8 alkoxy, aryloxy, arylalkoxy, aroyl,amino, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino andguanidino; R₅ is H or alkyl; R₆ is H, C1-8 alkyl, C3-7 cycloalkyl oraryl wherein R₆ is unsubstituted or substituted by one or more R_(f);R_(f) is selected from the group consisting of C1-8 alkyl, C3-7cycloalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, C1-8 alkoxy, aryloxy,arylC1-8alkoxy, heteroarylC1-8alkoxy, C1-8 alkoxycarbonyl,aryloxycarbonyl, C1-8 alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom is unsubstituted or independently mono or di-substitutedby C1-8 alkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl, or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, C1-8 alkanoylamino,aroylamino, C1-8 alkylthio wherein the sulfur atom is unoxidized oroxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom isunoxidized or oxidized to a sulfoxide or sulfone, arylC1-8 alkylthiowherein the sulfur atom is unoxidized or oxidized to a sulfoxide orsulfone, ureido wherein either nitrogen atom is unsubstituted orindependently substituted by alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, alkoxycarbonylamino, aryloxycarbonylamino, C1-8alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino,arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino whereinthe nitrogen atom is unsubstituted or independently mono ordi-substituted by alkyl, aryl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidinoand guanidino, R_(f) is unsubstituted or substituted by one or moreR_(g); R_(g) is selected from the group consisting of C1-8 alkyl, C3-7cycloalkyl, aryl unsubstituted or substituted by halogen, C1-3alkyl orC1-3alkoxy; heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, C1-8 alkoxy, aryloxy,arylC1-8alkoxy, C1-8 alkoxycarbonyl, aryloxycarbonyl, C1-8 alkanoyloxy,aroyloxy, carbamoyl wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by C1-8 alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl,triazolyl, tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl,pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, C1-8 alkanoylamino, aroylamino, C1-8 alkylthio whereinthe sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone,arylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, ureido wherein either nitrogen atom isunsubstituted or independently substituted by alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl,triazolyl, tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl,pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, alkoxycarbonylamino, aryloxycarbonylamino, C1-8alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino,arylsulfonylamino, alkylaminosulfonyl and arylaminosulfonyl, aminowherein the nitrogen atom is unsubstituted or independently mono ordi-substituted by alkyl, aryl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl, or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidinoand guanidino; R_(h) is selected from the group consisting of C1-8alkyl, aryl, C1-8 alkoxycarbonyl, aryloxycarbonyl,arylC1-8alkoxycarbonyl, carbamoyl wherein the nitrogen atom isunsubstituted or mono or di-substituted by C1-8 alkyl, C3-7 cycloalkyl,aryl, arylC1-8alkyl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl, or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, halogen, hydroxy, carboxyand cyano; R_(j) is selected from the group consisting of alkyl,cycloalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, arylalkyl, alkoxy, aryloxy,arylalkoxy, alkoxycarbonyl, aryloxycarbonyl, alkanoyloxy, aroyloxy,carbamoyl wherein the nitrogen atom is unsubstituted or independantlymono or di-susbstituted by alkyl, aryl, heterocyclyl selected from thegroup consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl; heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, alkanoylamino, aroylamino, alkylthio wherein thesulfur atom is unoxidized or oxidised to a sulfoxide or sulfone,arylthio wherein the sulfur atom is unoxidized or oxidised to asulfoxide or sulfone, arylalkylthio wherein the sulfur atom isunoxidized or oxidised to a sulfoxide or sulfone, ureido wherein eithernitrogen atom is unsubstituted or independently substituted by alkyl,aryl, heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl,heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl,oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyridinyl,pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl and phenoxazinyl, alkoxycarbonylamino,aryloxycarbonylamino, C1-8 alkylcarbamoyloxy, arylcarbamoyloxy,alkylsulfonylamino, arylsulfonylamino, alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom is unsubstituted orindependently mono or di-susbstituted by alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl; heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl,triazolyl, tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl,pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidinoand guanidino, R_(j) is unsubstituted or substituted by one or moreR_(k); R_(k) is selected from the group consisting of alkyl, cycloalkyl,aryl, heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl;heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl,oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyridinyl,pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl and phenoxazinyl, alkoxy, aryloxy, arylalkoxy,alkoxycarbonyl, aryloxycarbonyl, alkanoyloxy, aroyloxy, carbamoylwherein the nitrogen atom is unsubstituted or independantly mono ordi-susbstituted by alkyl, aryl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl, heteroaryl selected from furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl,oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyridinyl,pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl and phenoxazinyl, alkanoylamino, aroylamino, alkylthiowherein the sulfur atom is unoxidized or oxidised to a sulfoxide orsulfone, arylthio wherein the sulfur atom is unoxidized or oxidised to asulfoxide or sulfone, ureido wherein either nitrogen atom isunsubstituted or independently substituted by alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, heteroarylselected from furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, alkoxycarbonylamino, aryloxycarbonylamino,arylalkoxycarbonylamino, arylalkoxycarbonylaminoalkyl, C1-8alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino,arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino whereinthe nitrogen atom is unsubstituted or independently mono ordi-susbstituted by alkyl, aryl, heterocyclyl selected from pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl,heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl,oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyridinyl,pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl and phenoxazinyl, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino, wherein R_(k) is unsubstituted orsubstituted by R₁;  R₁ is selected from the group consisting of C1-5alkyl, C3-7 cycloalkyl, phenyl and benzyl; and X is O or S.
 13. Thecompound according to claim 12 wherein: Y is O or S; R₁ is pyrrolidinyl,piperidinyl, thiomorpholinyl, piperazinyl, furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl,pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl or quinoxalinyl wherein R₁ is unsubstituted or substitutedby one or more R_(b); R_(b) is selected from the group consisting ofC1-5 alkyl, C3-7 cycloalkyl, phenyl, naphthyl, heterocyclyl selectedfrom the group consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl, heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, quinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl,C1-5 alkoxy, aryloxy, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom isunsubstituted or independently mono or di-substituted by C1-8 alkyl,aryl, heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl,pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, C1-5 alkanoylamino, aroylamino, C1-5alkylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, arylthio wherein the sulfur atom is unoxidized oroxidized to a sulfoxide or sulfone, ureido wherein either nitrogen atomis unsubstituted or independently substituted by alkyl, aryl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl,pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, C1-5 alkoxycarbonylamino,aryloxycarbonylamino, C1-5 alkylcarbamoyloxy, arylcarbamoyloxy, C1-5alkylsulfonylamino, arylsulfonylamino, C1-5 alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl,pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino, R_(b) is unsubstituted or substituted byone or more R_(c); R_(c) is selected from the group consisting of C1-5alkyl, C3-6 cycloalkyl, aryl, heterocyclyl selected from the groupconsisting of piperidinyl, morpholinyl and piperazinyl; heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, tetrazolyl and pyridinyl, C1-5 alkoxy,aryloxy, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino andguanidino; R₂ is H or C1-3 alkyl; R₃ is H, C1-5 alkyl, C3-7 cycloalkylor aryl, wherein R₃ is unsubstituted or substituted by one or moreR_(d); R_(d) is selected from the group consisting of C1-5 alkyl, C3-7cycloalkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl,tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl,isoquinolinyl, quinazolinyl and quinoxalinyl, C1-5 alkoxy, aryloxy,C1-5alkanoyl, aroyl, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom isunsubstituted or independently mono or di-substituted by C1-5 alkyl,aryl, heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl,pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, C1-5 alkanoylamino, aroylamino, C1-5alkylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, arylthio wherein the sulfur atom is unoxidized oroxidized to a sulfoxide or sulfone, ureido wherein either nitrogen atomis unsubstituted or independently substituted by C1-5 alkyl, aryl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl orheteroaryl selected the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl,pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, C1-5 alkoxycarbonylamino,aryloxycarbonylamino, C1-5 alkylcarbamoyloxy, arylcarbamoyloxy, C1-5alkylsulfonylamino, arylsulfonylamino, C1-5 alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by C1-5 alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl,pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino, R_(d) is unsubstituted or substituted byone or more R_(e); R_(e) is selected from the group consisting of C1-5alkyl, C3-6 cycloalkyl, aryl, arylalkyl, C1-5 alkoxy, aryloxy,arylC1-5alkoxy, aroyl, amino, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino; R₄ is H or C1-3 alkyl; R₅ is H or C1-8alkyl; R₆ is H, C1-5 alkyl, C3-7 cycloalkyl or aryl wherein R₆ isunsubstituted or substituted by one or more R_(f); R_(f) is selectedfrom the group consisting of C1-5 alkyl, C3-7 cycloalkyl, aryl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl;heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl,pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, C1-5 alkoxy, aryloxy, arylC1-5alkoxy,heteroarylC1-5alkoxy, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom isunsubstituted or independently mono or di-substituted by C1-5 alkyl,aryl, heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl,pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, C1-5 alkanoylamino, aroylamino, C1-5alkylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, arylthio wherein the sulfur atom is unoxidized oroxidized to a sulfoxide or sulfone, arylC1-5 alkylthio wherein thesulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, ureidowherein either nitrogen atom is unsubstituted or independentlysubstituted by C1-5 alkyl, aryl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, quinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl,C1-5 alkoxycarbonylamino, aryloxycarbonylamino, C1-5 alkylcarbamoyloxy,arylcarbamoyloxy, C1-5 alkylsulfonylamino, arylsulfonylamino, C1-5alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atomis unsubstituted or independently mono or di-substituted by C1-5 alkyl,aryl, heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl,pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino, R_(f) is unsubstituted or substituted byone or more R_(g); R_(g) is selected from the group consisting of C1-5alkyl, C3-7 cycloalkyl, aryl unsubstituted or substituted by halogen,methyl or methoxy; heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl,tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl,isoquinolinyl, quinazolinyl and quinoxalinyl, C1-5 alkoxy, aryloxy,arylC1-5alkoxy, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy,aroyloxy, carbamoyl wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by C1-5 alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl,pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, C1-5 alkanoylamino, aroylamino, C1-5alkylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, arylthio wherein the sulfur atom is unoxidized oroxidized to a sulfoxide or sulfone, ureido wherein either nitrogen atomis unsubstituted or independently substituted by C1-5 alkyl, aryl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl,pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, C1-5 alkoxycarbonylamino,aryloxycarbonylamino, C1-5 alkylcarbamoyloxy, arylcarbamoyloxy, C1-5alkylsulfonylamino, arylsulfonylamino, C1-5 alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by C1-5 alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl,pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, halogen, hydroxy, oxo, carboxy, cyano,nitro, amidino and guanidino; R_(h) is selected from the groupconsisting of C1-5 alkyl, aryl, C1-5 alkoxycarbonyl, aryloxycarbonyl,arylC1-5alkoxycarbonyl, carbamoyl wherein the nitrogen atom isunsubstituted or mono or di-substituted with a group selected from C1-5alkyl, C3-7 cycloalkyl, aryl, arylC1-5alkyl, heterocyclyl selected fromthe group consisting of pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl or heteroaryl selected fromthe group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, quinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl,halogen, hydroxy, carboxy and cyano; R₁ is alkoxy, aryloxy or hydroxy;R₈ is a heteroaryl ring selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl,isoxazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl,triazinyl, indolizinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,indazolyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl,quinolizinyl, quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl,quinazolinyl, quinoxalinyl, naphthyridinyl, pteridinyl, carbazolyl,acridinyl and phenazinyl, wherein any of the above R₈ can beunsubstituted or substituted by one or more R_(j); R_(j) is selectedfrom the group consisting of C1-8alkyl, C3-7cycloalkyl, aryl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl;heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl,oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyridinyl,pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl,quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl,phenothiazinyl and phenoxazinyl; arylC1-8alkyl, C1-8alkoxy, aryloxy,arylC1-8alkoxy, C1-8alkoxycarbonyl, aryloxycarbonyl, C1-8alkanoyloxy,aroyloxy, carbamoyl wherein the nitrogen atom is unsubstituted orindependantly mono or di-susbstituted by C1-8alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl; heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl,triazolyl, tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl,pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, C1-8alkanoylamino, aroylamino, C1-8alkylthio whereinthe sulfur atom is unoxidized or oxidised to a sulfoxide or sulfone,arylthio wherein the sulfur atom is unoxidized or oxidised to asulfoxide or sulfone, arylC1-8alkylthio wherein the sulfur atom isunoxidized or oxidised to a sulfoxide or sulfone, ureido wherein eithernitrogen atom is unsubstituted or independently substituted by C1-8alkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, alkoxycarbonylamino,aryloxycarbonylamino, C1-8 alkylcarbamoyloxy, arylcarbamoyloxy,alkylsulfonylamino, arylsulfonylamino, alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom is unsubstituted orindependently mono or di-susbstituted by C1-8 alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl; heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl,triazolyl, tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl,pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidinoand guanidino, R_(j) is unsubstituted or substituted by one or moreR_(k); R_(k) is selected from the group consisting of C1-8 alkyl, C3-7cycloalkyl, aryl, heterocyclyl selected from pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl, heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl,triazolyl, tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl,pyrimidinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, C1-8 alkoxy, aryloxy, arylC1-8alkoxy,C1-8alkoxycarbonyl, aryloxycarbonyl, C1-8alkanoyloxy, aroyloxy,carbamoyl wherein the nitrogen atom is unsubstituted or independantlymono or di-susbstituted by C1-8alkyl, aryl, heterocyclyl selected frompyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl,carbazolyl, phenothiazinyl and phenoxazinyl, alkanoylamino, aroylamino,C1-8alkylthio wherein the sulfur atom is unoxidized or oxidised to asulfoxide or sulfone, arylthio wherein the sulfur atom is unoxidized oroxidised to a sulfoxide or sulfone, ureido wherein either nitrogen atomis unsubstituted or independently substituted by C1-8alkyl, aryl,heterocyclyl selected from pyrrolidinyl, piperidinyl, morpholinyl,thiomorpholinyl, piperazinyl and indolinyl, heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl,pyrazinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolinyl,isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenothiazinyland phenoxazinyl, C1-8alkoxycarbonylamino, aryloxycarbonylamino,arylC1-8alkoxycarbonylamino, arylalkoxycarbonylaminoC1-8alkyl, C1-8alkylcarbamoyloxy, arylcarbamoyloxy, C1-8alkylsulfonylamino,arylsulfonylamino, C1-8alkylaminosulfonyl, arylaminosulfonyl, aminowherein the nitrogen atom is unsubstituted or independently mono ordi-susbstituted by C1-8alkyl, aryl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl; heteroaryl selected from the group consistingof furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl,isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl,thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl,isoindolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, purinyl, quinolinyl, isoquinolinyl, quinazolinyl,quinoxalinyl, carbazolyl, phenothiazinyl and phenoxazinyl, halogen,hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino, whereinR_(k) is unsubstituted or substituted by R₁.
 14. The compound accordingto claim 13 wherein: Y is O; R₁ is piperidinyl, thiomorpholinyl,piperazinyl, furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl orisoquinolinyl, wherein R₁ is unsubstituted or substituted by one or moreR_(b); R_(b) is selected from the group consisting of C1-5 alkyl, C3-7cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl,piperazinyl and indolinyl; heteroaryl selected from the group consistingof furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl,tetrazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl andisoquinolinyl; C1-5 alkoxy, aryloxy, C1-5 alkoxycarbonyl,aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom is unsubstituted or independently mono or di-substitutedby C1-5 alkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl andindolinyl, or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, tetrazolyl,pyridinyl, indolyl, benzofuranyl, benzothienyl, benzimidazolyl,benzthiazolyl, benzoxazolyl, quinolinyl and isoquinolinyl, C1-5alkanoylamino, aroylamino, C1-5 alkylthio wherein the sulfur atom isunoxidized or oxidized to a sulfoxide or sulfone, arylthio wherein thesulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, ureidowherein either nitrogen atom is unsubstituted or independentlysubstituted by alkyl or aryl; C1-5 alkoxycarbonylamino,aryloxycarbonylamino, C1-5 alkylcarbamoyloxy, arylcarbamoyloxy, C1-5alkylsulfonylamino, arylsulfonylamino, C1-5 alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by alkyl, aryl, heterocyclylselected from the group consisting of pyrrolidinyl, piperidinyl,morpholinyl, thiomorpholinyl, piperazinyl and indolinyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyland isoquinolinyl, halogen, hydroxy, oxo, carboxy, cyano and nitro,R_(b) is unsubstituted or substituted by one or more R_(c); R_(c) isselected from the group consisting of C1-5 alkyl, C3-6 cycloalkyl, aryl,C1-5 alkoxy, aryloxy, halogen, hydroxy, oxo, carboxy and cyano; R₂ is Hor methyl; R₃ is H, C1-5 alkyl, C3-7 cycloalkyl or phenyl, wherein R₃ isunsubstituted or substituted by one or more R_(d); R_(d) is selectedfrom the group consisting of C1-3 alkyl, C3-6 cycloalkyl, phenyl,naphthyl, heterocyclyl selected from the group consisting ofpiperidinyl, morpholinyl and piperazinyl; heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl andisoquinolinyl, C1-5 alkoxy, aryloxy, aroyl, C1-5 alkoxycarbonyl,aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom is unsubstituted or independently mono or di-substitutedby C1-5 alkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl and piperazinyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyland isoquinolinyl, C1-5 alkanoylamino, aroylamino, C1-5 alkylthiowherein the sulfur atom is unoxidized or oxidized to a sulfoxide orsulfone, arylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, ureido wherein either nitrogen atom isunsubstituted or independently substituted by C1-5 alkyl, phenyl,naphthyl, heterocyclyl selected from the group consisting ofpiperidinyl, morpholinyl and piperazinyl or heteroaryl selected thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl andisoquinolinyl, C1-5 alkoxycarbonylamino, aryloxycarbonylamino, C1-5alkylcarbamoyloxy, arylcarbamoyloxy, C1-5 alkylsulfonylamino,arylsulfonylamino, C1-5 alkylaminosulfonyl, arylaminosulfonyl, aminowherein the nitrogen atom is unsubstituted or independently mono ordi-substituted by C1-5 alkyl, phenyl, naphthyl, heterocyclyl selectedfrom the group consisting of piperidinyl, morpholinyl and piperazinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,quinolinyl and isoquinolinyl, halogen, hydroxy, oxo, carboxy and cyano,R_(d) is unsubstituted or substituted by one or more R_(e); R_(e) isselected from the group consisting of C1-5 alkyl, C3-6 cycloalkyl, aryl,arylC1-5alkyl, C1-5 alkoxy, aryloxy, arylC1-3alkoxy, aroyl, amino,halogen, hydroxy, oxo, carboxy and cyano; R₄ is H or methyl; R₅ is H orC1-5 alkyl; R₆ is H, C1-5 alkyl, C3-7 cycloalkyl, phenyl or naphthylwherein R₆ is unsubstituted or substituted by one or more R_(f); R_(f)is selected from the group consisting of C1-5 alkyl, C3-7 cycloalkyl,phenyl, naphthyl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl andindolinyl; heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl,tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl,isoquinolinyl, quinazolinyl and quinoxalinyl, C1-5 alkoxy, aryloxy,arylC1-5alkoxy, pyridylC1-5alkoxy, thienylC1-5 alkoxy,furanylC1-5alkoxy, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom isunsubstituted or independently mono or di-substituted by C1-5 alkyl,aryl, heterocyclyl selected from the group consisting of piperidinyl,morpholinyl and piperazinyl or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl andisoquinolinyl, C1-5 alkanoylamino, aroylamino, C1-5 alkylthio whereinthe sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone,arylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, arylC1-5 alkylthio wherein the sulfur atom isunoxidized or oxidized to a sulfoxide or sulfone, ureido wherein eithernitrogen atom is unsubstituted or independently substituted by C1-5alkyl, aryl, heterocyclyl selected from the group consisting ofpiperidinyl, morpholinyl and piperazinyl or heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl andisoquinolinyl, C1-5 alkoxycarbonylamino, aryloxycarbonylamino, C1-5alkylcarbamoyloxy, arylcarbamoyloxy, C1-5 alkylsulfonylamino,arylsulfonylamino, C1-5 alkylaminosulfonyl, arylaminosulfonyl, aminowherein the nitrogen atom is unsubstituted or independently mono ordi-substituted by C1-5 alkyl, aryl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl and piperazinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,quinolinyl and isoquinolinyl, halogen, hydroxy, oxo, carboxy and cyano,R_(f) is unsubstituted or substituted by one or more R_(g); R_(g) isselected from the group consisting of C1-5 alkyl, C3-7 cycloalkyl,phenyl unsubstituted or substituted by halogen, methyl or methoxy;naphthyl unsubstituted or substituted by halogen, methyl or methoxy;heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl and indolinyl;heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl,pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinazolinyl and quinoxalinyl, C1-5 alkoxy, aryloxy, arylC1-5alkoxy,C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy,carbamoyl wherein the nitrogen atom is unsubstituted or independentlymono or di-substituted by C1-5 alkyl, aryl, heterocyclyl selected fromthe group consisting of piperidinyl, morpholinyl and piperazinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,quinolinyl and isoquinolinyl, C1-5 alkanoylamino, aroylamino, C1-5alkylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, arylthio wherein the sulfur atom is unoxidized oroxidized to a sulfoxide or sulfone, ureido wherein either nitrogen atomis unsubstituted or independently substituted by C1-5 alkyl, aryl,heterocyclyl selected from the group consisting of piperidinyl,morpholinyl and piperazinyl or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl andisoquinolinyl, C1-5 alkoxycarbonylamino, aryloxycarbonylamino, C1-5alkylcarbamoyloxy, arylcarbamoyloxy, C1-5 alkylsulfonylamino,arylsulfonylamino, C1-5 alkylaminosulfonyl, arylaminosulfonyl, aminowherein the nitrogen atom is unsubstituted or independently mono ordi-substituted by C1-5 alkyl, aryl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl and piperazinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,quinolinyl and isoquinolinyl, halogen, hydroxy, oxo, carboxy and cyano;R_(h) is selected from the group consisting of C1-5 alkyl, phenyl,naphthyl, C1-5 alkoxycarbonyl, aryloxycarbonyl, arylC1-3alkoxycarbonyl,carbamoyl wherein the nitrogen atom is unsubstituted or mono ordi-substituted by C1-5 alkyl, C3-6 cycloalkyl, phenyl, naphthyl,arylC1-3alkyl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl and piperazinyl or heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyland isoquinolinyl, halogen, hydroxy, carboxy and cyano; Z is O or S;R_(j) is selected from the group consisting of C1-5alkyl,C3-6cycloalkyl, phenyl, naphthyl, heterocyclyl selected from the groupconsisting of pyrrolidinyl, piperidinyl, morpholinyl and piperazinyl;heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, tetrazolyl, pyridinyl,pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyland isoquinolinyl, arylC1-5alkyl, C1-5alkoxy, aryloxy, arylC1-5alkoxy,C1-5alkoxycarbonyl, aryloxycarbonyl, C1-5alkanoyloxy, aroyloxy,carbamoyl wherein the nitrogen atom is unsubstituted or independantlymono or di-susbstituted by C1-5alkyl, aryl, heterocyclyl selected fromthe group consisting of piperidinyl, morpholinyl and piperazinyl,heteroaryl selected from furanyl, thienyl, pyrrolyl, oxazolyl,thiazolyl, imidazolyl, tetrazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyland isoquinolinyl, C1-5alkanoylamino, aroylamino, C1-5alkylthio whereinthe sulfur atom is unoxidized or oxidised to a sulfoxide or sulfone,arylthio wherein the sulfur atom is unoxidized or oxidised to asulfoxide or sulfone, arylC1-5alkylthio wherein the sulfur atom isunoxidized or oxidised to a sulfoxide or sulfone, ureido wherein eithernitrogen atom is unsubstituted or independently substituted by C1-5alkyl, aryl, heterocyclyl selected from the group consisting ofpiperidinyl, morpholinyl and piperazinyl; heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, tetrazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl andisoquinolinyl, C1-5alkoxycarbonylamino, aryloxycarbonylamino, C1-5alkylcarbamoyloxy, arylcarbamoyloxy, C1-5alkylsulfonylamino,arylsulfonylamino, C1-5alkylaminosulfonyl, arylaminosulfonyl, aminowherein the nitrogen atom is unsubstituted or independently mono ordi-susbstituted by C1-5 alkyl, aryl, heterocyclyl selected from thegroup consisting of piperidinyl, morpholinyl and piperazinyl; heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, tetrazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,purinyl, quinolinyl and isoquinolinyl, halogen, hydroxy, oxo, carboxy,cyano, nitro, amidino and guanidino, wherein R_(j) is unsubstituted orsubstituted by one or more R_(k); R_(k) is selected from the groupconsisting of C1-3 alkyl, C3-6 cycloalkyl, phenyl, naphthyl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl and piperazinyl; heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, tetrazolyl, pyridinyl,pyridazinyl, pyrimidinyl and pyrazinyl, C1-3 alkoxy, aryloxy, arylC1-3alkoxy, C1-3 alkoxycarbonyl, aryloxycarbonyl, C1-3 alkanoyloxy,aroyloxy, carbamoyl wherein the nitrogen atom is unsubstituted orindependantly mono or di-susbstituted by C1-3 alkyl, aryl, heterocyclylselected from the group consisting of morpholinyl and piperazinyl;heteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, tetrazolyl and pyridinyl,C1-3alkanoylamino, aroylamino, C1-3alkylthio wherein the sulfur atom isunoxidized or oxidised to a sulfoxide or sulfone, arylthio wherein thesulfur atom is unoxidized or oxidised to a sulfoxide or sulfone, ureidowherein either nitrogen atom is unsubstituted or independentlysubstituted by C1-3alkyl, phenyl, naphthyl, heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, tetrazolyl and pyridinyl, C1-3alkoxycarbonylamino,aryloxycarbonylamino, arylC1-3 alkoxycarbonylamino,benzyloxycarbonylaminoC1-5 alkyl, C1-3 alkylcarbamoyloxy,arylcarbamoyloxy, C1-3alkylsulfonylamino, arylsulfonylamino,C1-3alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogenatom is unsubstituted or independently mono or di-susbstituted byC1-3alkyl, aryl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl and piperazinyl; heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, tetrazolyl, pyridinyl, pyridazinyl,pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl andisoquinolinyl, halogen, hydroxy, oxo, carboxy, cyano and nitro, whereinR_(k) is unsubstituted or substituted by R₁; and R₁ is selected from thegroup consisting of C1-5 alkyl, C3-7 cycloalkyl and phenyl.
 15. Thecompound according to claim 14 wherein: R₁ is piperidinyl, piperazinyl,furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl,indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl,benzoxazolyl, quinolinyl or isoquinolinyl, wherein R₁ is unsubstitutedor substituted by one or more R_(b); R_(b) is selected from the groupconsisting of C1-3 alkyl, C3-6 cycloalkyl, phenyl, naphthyl,heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl and piperazinyl, heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, tetrazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl andisoquinolinyl, C1-3 alkoxy, phenoxy, C1-3 alkoxycarbonyl,aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom is unsubstituted or independently mono or di-substitutedby C1-5 alkyl, phenyl or heteroaryl selected from the group consistingof furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl,pyridinyl, indolyl, benzofuranyl, benzothienyl, benzimidazolyl,benzthiazolyl, benzoxazolyl, quinolinyl and isoquinolinyl, C1-5alkanoylamino, aroylamino, C1-5 alkylthio wherein the sulfur atom isunoxidized or oxidized to a sulfoxide or sulfone, arylthio wherein thesulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, ureidowherein either nitrogen atom is unsubstituted or independentlysubstituted by C1-5 alkyl, phenyl or naphthyl; C1-5 alkoxycarbonylamino,C1-5 alkylcarbamoyloxy, arylcarbamoyloxy, C1-5 alkylsulfonylamino,arylsulfonylamino, C1-5 alkylaminosulfonyl, arylaminosulfonyl, aminowherein the nitrogen atom is unsubstituted or independently mono ordi-substituted by C1-5alkyl, phenyl, naphthyl, heterocyclyl selectedfrom the group consisting of piperidinyl, morpholinyl and piperazinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,quinolinyl and isoquinolinyl, halogen, hydroxy, oxo, carboxy and cyano,R_(b) is unsubstituted or substituted by one or more R_(c); R_(c) isselected from the group consisting of C1-3 alkyl, C5-6 cycloalkyl, aryl,C1-3 alkoxy, phenoxy, halogen, hydroxy, oxo, carboxy and cyano; R₂ is H;R₃ is C1-5 alkyl, C3-6 cycloalkyl or phenyl, wherein R₃ is unsubstitutedor substituted by one or more R_(d); R_(d) is selected from the groupconsisting of C1-3 alkyl, C3-6 cycloalkyl, phenyl, naphthyl,heterocyclyl selected from the group consisting of piperidinyl,morpholinyl and piperazinyl; heteroaryl selected from the groupconsisting of furanyl, thienyl, thiazolyl, imidazolyl, pyridinyl,indolyl, quinolinyl and isoquinolinyl, C1-5 alkoxy, phenoxy, aroyl, C1-5alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoylwherein the nitrogen atom is unsubstituted or independently mono ordi-substituted by C1-5 alkyl, phenyl, naphthyl, heterocyclyl selectedfrom the group consisting of piperidinyl, morpholinyl and piperazinyl orheteroaryl selected from the group consisting of furanyl, thienyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl and indolyl, C1-5alkanoylamino, aroylamino, C1-3 alkylthio wherein the sulfur atom isunoxidized or oxidized to a sulfoxide or sulfone, phenylthio wherein thesulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, ureidowherein either nitrogen atom is unsubstituted or independentlysubstituted by C1-3 alkyl, phenyl or heteroaryl selected the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl and indolyl, C1-5 alkoxycarbonylamino, C1-5alkylcarbamoyloxy, arylcarbamoyloxy, C1-5 alkylsulfonylamino,arylsulfonylamino, amino wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by C1-3 alkyl, phenyl, heterocyclylselected from the group consisting of piperidinyl, morpholinyl andpiperazinyl or heteroaryl selected from the group consisting of furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl andindolyl, halogen, hydroxy, oxo, carboxy and cyano, R_(d) isunsubstituted or substituted by one or more R_(e); R_(e) is selectedfrom the group consisting of C1-5 alkyl, C5-6 cycloalkyl, phenyl,naphthyl, arylC1-3alkyl, C1-5 alkoxy, phenoxy, arylC1-3alkoxy, aroyl,amino, halogen, hydroxy, oxo, carboxy and cyano; wherein theconfiguration at the stereocenter defined by R₂ and R₃ and the carbonthey are attached to is the L enantiomer; R₄ is H; R₅ is H or C1-3alkyl; R₆ is H, C1-5 alkyl, C3-6 cycloalkyl or phenyl, wherein R₆ isunsubstituted or substituted by one or more R_(f); R_(f) is selectedfrom the group consisting of C1-3 alkyl, C3-6 cycloalkyl, phenyl,naphthyl, heterocyclyl selected from the group consisting ofpyrrolidinyl, piperidinyl, morpholinyl and piperazinyl; heteroarylselected from the group consisting of furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyland isoquinolinyl, C1-5 alkoxy, aryloxy, arylC1-3alkoxy,pyridylC1-5alkoxy, thienylC1-5alkoxy, furanylC1-5alkoxy, C1-5alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy, carbamoylwherein the nitrogen atom is unsubstituted or independently mono ordi-substituted by C1-5 alkyl, phenyl or heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl and indolyl, C1-5 alkanoylamino, aroylamino, C1-3alkylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, arylthio wherein the sulfur atom is unoxidized oroxidized to a sulfoxide or sulfone, arylC1-3alkylthio wherein the sulfuratom is unoxidized or oxidized to a sulfoxide or sulfone, ureido whereineither nitrogen atom is unsubstituted or independently substituted byC1-5 alkyl or phenyl; C1-5 alkoxycarbonylamino, C1-5 alkylsulfonylamino,arylsulfonylamino, amino wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by C1-5 alkyl, phenyl, naphthyl,heterocyclyl selected from the group consisting of piperidinyl,morpholinyl and piperazinyl or heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl and indolyl, halogen, hydroxy, oxo, carboxy andcyano, R_(f) is unsubstituted or substituted by one or more R_(g); R_(g)is selected from the group consisting of C1-3 alkyl, C5-6 cycloalkyl,phenyl unsubstituted or substituted by halogen, methyl or methoxy;heterocyclyl selected from the group consisting of pyrrolidinyl,piperidinyl, morpholinyl and piperazinyl; heteroaryl selected from thegroup consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyridinyl, pyrimidinyl, pyrazinyl and indolyl, C1-5 alkoxy,aryloxy, arylC1-3alkoxy, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom isunsubstituted or independently mono or di-substituted by C1-5 alkyl oraryl; C1-5 alkanoylamino, aroylamino, C1-5 alkylthio wherein the sulfuratom is unoxidized or oxidized to a sulfoxide or sulfone, arylthiowherein the sulfur atom is unoxidized or oxidized to a sulfoxide orsulfone, ureido wherein either nitrogen atom is unsubstituted orindependently substituted by C1-5 alkyl or aryl; C1-5alkoxycarbonylamino, aryloxycarbonylamino, C1-5 alkylcarbamoyloxy,arylcarbamoyloxy, C1-5 alkylsulfonylamino, arylsulfonylamino, C1-5alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atomis unsubstituted or independently mono or di-substituted by C1-5 alkylor aryl; halogen, hydroxy, oxo, carboxy and cyano; R_(h) is selectedfrom the group consisting of C1-5 alkyl, phenyl, C1-5 alkoxycarbonyl,aryloxycarbonyl, arylC1-3alkoxycarbonyl, carbamoyl wherein the nitrogenatom is unsubstituted or mono or di-substituted with C1-5 alkyl, C3-6cycloalkyl, phenyl, naphthyl or arylC1-3alkyl, halogen, hydroxy, carboxyand cyano; Z is O; R₈ is a heteroaryl ring selected from the groupconsisting of oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl,isothiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,quinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl, wherein any ofthe above R₈ can be unsubstituted or substituted by one or more R_(j);R_(j) is selected from the group consisting of C1-5 alkyl, C5-6cycloalkyl, phenyl, naphthyl, pyrrolidinyl, piperidinyl, morpholinyl,piperazinyl, furanyl, thienyl, pyrrolyl, tetrazolyl, pyridinyl,pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,arylC1-3alkyl, C1-3alkoxy, aryloxy, arylC1-3alkoxy, C1-3alkoxycarbonyl,aryloxycarbonyl, C1-3alkanoyloxy, aroyloxy, carbamoyl wherein thenitrogen atom is unsubstituted or independantly mono or di-susbstitutedby C1-3alkyl, phenyl, naphthyl, piperidinyl, furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, tetrazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl,quinolinyl and isoquinolinyl; C1-3alkanoylamino, aroylamino,C1-3alkylthio wherein the sulfur atom is unoxidized or oxidised to asulfoxide or sulfone, arylthio wherein the sulfur atom is unoxidized oroxidised to a sulfoxide or sulfone, arylC1-3alkylthio wherein the sulfuratom is unoxidized or oxidised to a sulfoxide or sulfone, ureido whereineither nitrogen atom is unsubstituted or independently substituted byC1-3 alkyl, phenyl, naphthyl, piperidinyl, morpholinyl, thiazolyl,imidazolyl, tetrazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl andisoquinolinyl; C1-3 alkoxycarbonylamino, aryloxycarbonylamino, C1-3alkylcarbamoyloxy, arylcarbamoyloxy, C1-3alkylsulfonylamino,arylsulfonylamino, C1-3alkylaminosulfonyl, arylaminosulfonyl, aminowherein the nitrogen atom is unsubstituted or independently mono ordi-susbstituted by C1-3 alkyl, phenyl, naphthyl, piperidinyl, furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, tetrazolyl,pyridinyl, indolyl, benzofuranyl, benzothienyl, benzimidazolyl,benzthiazolyl, benzoxazolyl, quinolinyl and isoquinolinyl; halogen,hydroxy, oxo, carboxy, cyano and nitro, R_(j) is unsubstituted orsubstituted by one or more R_(k); R_(k) is selected from the groupconsisting of methyl, C5-6 cycloalkyl, phenyl, pyrrolidinyl,piperidinyl, morpholinyl, piperazinyl, furanyl, thienyl, pyrrolyl,tetrazolyl, pyridinyl, pyrimidinyl, C1-3 alkoxy, phenoxy, benzyloxy,methoxycarbonyl, acetyloxy, benzoyloxy, carbamoyl wherein the nitrogenatom is unsubstituted or independantly mono or di-susbstituted by C1-3alkyl, phenyl, furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl or pyridinyl; acetylamino, benzoylamino, methylthio whereinthe sulfur atom is unoxidized or oxidised to a sulfoxide or sulfone,ureido wherein either nitrogen atom is unsubstituted or independentlysubstituted by methyl, phenyl, furanyl, thienyl, pyrrolyl, oxazolyl,thiazolyl, imidazolyl or pyridinyl; arylC1-3 alkoxycarbonylamino,benzyloxycarbonylaminoC1-5alkyl, methylcarbamoyloxy, amino wherein thenitrogen atom is unsubstituted or independently mono or di-susbstitutedby C1-3alkyl, phenyl, naphthyl, pyrrolidinyl, piperidinyl, furanyl,thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl,pyrimidinyl, indolyl, benzofuranyl, benzothienyl, benzimidazolyl,benzthiazolyl, benzoxazolyl, quinolinyl or isoquinolinyl, halogen,hydroxy, oxo, carboxy, cyano and nitro, wherein R_(k) is unsubstitutedor substituted by R₁; R₁ is selected from the group consisting of C1-3alkyl, C3-6 cycloalkyl and phenyl.
 16. The compound according to claim15 wherein: R₁ is piperidinyl, piperazinyl, furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl, pyridinyl or indolyl, wherein R₁ isunsubstituted or substituted by one or more R_(b); R_(b) is selectedfrom the group consisting of C1-3 alkyl, C5-6 cycloalkyl, phenyl,heterocyclyl selected from the group consisting of piperidinyl,morpholinyl and piperazinyl; heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl, imidazolyl, tetrazolyl,pyridinyl, indolyl, benzofuranyl, benzothienyl, benzimidazolyl,benzthiazolyl, benzoxazolyl, quinolinyl and isoquinolinyl, C1-3 alkoxy,C1-3 alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy, aroyloxy,carbamoyl wherein the nitrogen atom is unsubstituted or independentlymono or di-substituted by C1-3 alkyl, phenyl or heteroaryl selected fromthe group consisting of pyrrolyl, imidazolyl, pyridinyl, indolyl,benzofuranyl, benzothienyl, benzimidazolyl and benzthiazolyl; C1-5alkanoylamino, aroylamino, C1-3 alkylthio wherein the sulfur atom isunoxidized or oxidized to a sulfoxide or sulfone, arylthio wherein thesulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, ureidowherein either nitrogen atom is unsubstituted or independentlysubstituted by C1-3alkyl or phenyl; C1-5 alkylsulfonylamino,arylsulfonylamino, amino wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by C1-3alkyl, phenyl, heterocyclylselected from the group consisting of piperidinyl, morpholinyl andpiperazinyl or heteroaryl selected from the group consisting ofpyrrolyl, imidazolyl, pyridinyl, indolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl andisoquinolinyl; halogen, hydroxy, oxo, carboxy and cyano, R_(b) isunsubstituted or substituted by one or more R_(c); R_(c) is selectedfrom the group consisting of C1-3 alkyl, C5-6 cycloalkyl, C1-3 alkoxy,halogen and hydroxy; R₃ is C1-5 alkyl, C5-6 cycloalkyl or phenyl whereinR₃ is unsubstituted or substituted by one or more R_(d); R_(d) isselected from the group consisting of C1-3 alkyl, C3-6 cycloalkyl,phenyl, naphthyl, 4-piperidinyl, 4-morpholinyl, piperazinyl, furanyl,thienyl, thiazolyl, imidazolyl, pyridinyl, indolyl, C1-5 alkoxy,phenoxy, aroyl, C1-5 alkoxycarbonyl, aryloxycarbonyl, C1-5 alkanoyloxy,aroyloxy, carbamoyl wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by C1-5 alkyl or phenyl; C1-5alkanoylamino, C1-3 alkylthio wherein the sulfur atom is unoxidized oroxidized to a sulfoxide or sulfone, ureido wherein either nitrogen atomis unsubstituted or independently substituted by C1-3 alkyl or phenyl;C1-5 alkoxycarbonylamino, C1-5 alkylsulfonylamino, arylsulfonylamino,amino wherein the nitrogen atom is unsubstituted or independently monoor di-substituted by C1-3 alkyl or phenyl; halogen, hydroxy, oxo,carboxy and cyano, R_(d) is unsubstituted or substituted by one or moreR_(e); R_(e) is selected from the group consisting of C1-5 alkyl, C5-6cycloalkyl, phenyl, benzyl, C1-5 alkoxy, phenoxy, benzyloxy, aroyl,halogen, hydroxy, oxo, carboxy and cyano; R₆ is H, C1-5 alkyl or phenylwherein R₆ is unsubstituted or substituted by one or more R_(f); R_(f)is selected from the group consisting of C1-3 alkyl, C3-6 cycloalkyl,phenyl, naphthyl, furanyl, thienyl, thiazolyl, imidazolyl, pyridinyl,indolyl, C1-3 alkoxy, benzyloxy, pyridyl, C1-3alkoxy, thienylC1-3alkoxy,furanylC1-3alkoxy, C1-3 alkoxycarbonyl, phenoxyoxycarbonyl, C1-5alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom isunsubstituted or independently mono or di-substituted by C1-3 alkyl orphenyl; C1-5 alkanoylamino, aroylamino, methylthio wherein the sulfuratom is unoxidized or oxidized to a sulfoxide or sulfone, benzylthiowherein the sulfur atom is unoxidized or oxidized to a sulfoxide orsulfone, ureido wherein either nitrogen atom is unsubstituted orindependently substituted by C1-5 alkyl or phenyl; C1-3alkoxycarbonylamino, amino wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by C1-5 alkyl or phenyl; halogen,hydroxy, oxo, carboxy and cyano, R_(f) is unsubstituted or substitutedby one or more R_(g); R_(g) is selected from the group consisting ofC1-3 alkyl, phenyl unsubstituted or substituted by halogen, methyl ormethoxy; heterocyclyl selected from the group consisting of piperidinyl,morpholinyl and piperazinyl; heteroaryl selected from the groupconsisting of furanyl, thienyl, pyrrolyl and pyridinyl, C1-3 alkoxy,aryloxy, benzyloxy, C1-5 alkoxycarbonyl, C1-5 alkanoyloxy, aroyloxy,carbamoyl wherein the nitrogen atom is unsubstituted or independentlymono or di-substituted by C1-5 alkyl or phenyl; C1-5 alkanoylamino,aroylamino, C1-5 alkylthio wherein the sulfur atom is unoxidized oroxidized to a sulfoxide or sulfone, ureido wherein either nitrogen atomis unsubstituted or independently substituted by C1-5 alkyl or phenyl;C1-5 alkoxycarbonylamino, C1-5 alkylcarbamoyloxy, arylcarbamoyloxy, C1-3alkylsulfonylamino, arylsulfonylamino, C1-3 alkylaminosulfonyl,arylaminosulfonyl, amino wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by C1-3 alkyl or phenyl; halogen,hydroxy, oxo, carboxy and cyano; R_(h) is selected from the groupconsisting of C1-3 alkyl, phenyl, C1-3 alkoxycarbonyl,phenoxyoxycarbonyl, benzyloxy, carbamoyl wherein the nitrogen atom isunsubstituted or mono or di-substituted with C1-5 alkyl, phenyl orbenzyl, halogen, hydroxy, carboxy and cyano; R₈ is a heteroaryl ringselected from the group consisting of oxazolyl, thiazolyl, imidazolyl,pyridyl, indolyl, benzofuranyl, benzothienyl, benzimidazolyl,benzthiazolyl, benzoxazolyl, quinolinyl and isoquinolinyl, wherein anyof the above R₈ can be unsubstituted or substituted by one or moreR_(j); R_(j) is selected from the group consisting of C1-5 alkyl, C5-6cycloalkyl, phenyl, naphthyl, pyrrolidinyl, piperidinyl, morpholinyl,piperazinyl, furanyl, thienyl, pyrrolyl, tetrazolyl, pyridinyl,pyrimidinyl, benzyl, C1-3alkoxy, phenoxy, benzyloxy, C1-3alkoxycarbonyl,acetyloxy, benzoyloxy, carbamoyl wherein the nitrogen atom isunsubstituted or independantly mono or di-substituted by methyl, phenyl,furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl orpyridinyl; acetylamino, benzoylamino, methylthio wherein the sulfur atomis unoxidized or oxidised to a sulfoxide or sulfone, benzylthio whereinthe sulfur atom is unoxidized or oxidised to a sulfoxide or sulfone,ureido wherein either nitrogen atom is unsubstituted or independentlysubstituted by methyl, phenyl, thiazolyl, imidazolyl or pyridinyl; C1-3alkoxycarbonylamino, C1-3 alkylcarbamoyloxy, arylcarbamoyloxy,C1-3alkylsulfonylamino, arylsulfonylamino, amino wherein the nitrogenatom is unsubstituted or independently mono or di-susbstituted bymethyl, phenyl, furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl or pyridinyl; halogen, hydroxy, carboxy, cyano and nitro,R_(j) is unsubstituted or substituted by one or more R_(k); R_(k) isselected from the group consisting of methyl, C5-6 cycloalkyl, phenyl,pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, furanyl, thienyl,pyrrolyl, pyridinyl, C1-3 alkoxy, phenoxy, benzyloxy, methoxycarbonyl,acetyloxy, benzoyloxy, carbamoyl wherein the nitrogen atom isunsubstituted or independantly mono or di-susbstituted by methyl,phenyl, furanyl, thienyl; acetylamino, benzoylamino, methylthio whereinthe sulfur atom is unoxidized or oxidised to a sulfoxide or sulfone,ureido wherein either nitrogen atom is unsubstituted or independentlysubstituted by methyl, phenyl, furanyl, thienyl, pyrrolyl, oxazolyl andthiazolyl, benzyloxycarbonylamino, benzyloxycarbonylaminoC1-5 alkyl,amino wherein the nitrogen atom is unsubstituted or independently monoor di-susbstituted by C1-3alkyl, phenyl, furanyl, thienyl, pyrrolyl,oxazolyl, thiazolyl, imidazolyl and pyridinyl, halogen, hydroxy,carboxy, cyano and nitro, wherein R_(k) is unsubstituted or substitutedby R₁; R₁ is selected from the group consisting of C1-3 alkyl, C3-6cycloalkyl and phenyl.
 17. The compound according to claim 16 wherein:R₁ is piperidinyl, piperazinyl, furanyl, thienyl or pyrrolyl, wherein R₁is unsubstituted or substituted by one or more R_(b); R_(b) is selectedfrom the group consisting of C1-3 alkyl, C5-6 cycloalkyl, phenyl,furanyl, thienyl, pyrrolyl, imidazolyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, C1-3 alkoxy,C1-3 alkoxycarbonyl, carbamoyl wherein the nitrogen atom isunsubstituted or independently mono or di-substituted by C1-3 alkyl orphenyl; C1-5 alkanoylamino, aroylamino, ureido wherein either nitrogenatom is unsubstituted or independently substituted by C1-3alkyl orphenyl; C1-5 alkylsulfonylamino, arylsulfonylamino, amino wherein thenitrogen atom is unsubstituted or independently mono or di-substitutedby C1-3alkyl or phenyl;, halogen, hydroxy, oxo, carboxy and cyano, R_(b)is unsubstituted or substituted by one or more R_(c); R_(c) is selectedfrom the group consisting of C1-3 alkyl, C1-3 alkoxy, halogen andhydroxy; R_(d) is selected from the group consisting of C1-3 alkyl, C3-6cycloalkyl, phenyl, naphthyl, 4-piperidinyl, furanyl, thienyl,thiazolyl, imidazolyl, pyridinyl, indolyl, C1-3alkoxy,C1-5alkoxycarbonyl, C1-5alkanoyloxy, benzoyloxy, carbamoyl wherein thenitrogen atom is unsubstituted or independently mono or di-substitutedby C1-3alkyl or phenyl; C1-5alkanoylamino, C1-3 alkylthio wherein thesulfur atom is unoxidized or oxidized to a sulfoxide or sulfone,C1-3alkoxycarbonylamino, C1-3alkylsulfonylamino, amino wherein thenitrogen atom is unsubstituted or independently mono or di-substitutedby C1-3 alkyl or phenyl, halogen, hydroxy, oxo, carboxy and cyano, R_(d)is unsubstituted or substituted by one or more R_(e); R_(e) is selectedfrom the group consisting of C1-3 alkyl, phenyl, benzyl, C1-3 alkoxy,phenoxy, benzyloxy, benzoyl, halogen, hydroxy, oxo, carboxy and cyano;R₅ is H or methyl; R₆ is C1-5 alkyl or phenyl, wherein R₆ isunsubstituted or substituted by one or more groups of the formula R_(f),R_(f) is selected from the group consisting of methyl, C3-6 cycloalkyl,phenyl, naphthyl, furanyl, thienyl, thiazolyl, imidazolyl, pyridinyl,indolyl, C1-3 alkoxy, benzyloxy, C1-5 alkanoylamino, aroylamino,methylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, benzylthio wherein the sulfur atom is unoxidizedor oxidized to a sulfoxide or sulfone, C1-3 alkoxycarbonylamino, aminowherein the nitrogen atom is unsubstituted or independently mono ordi-substituted by C1-5 alkyl or phenyl; halogen, hydroxy, oxo, carboxyand cyano, R_(f) is unsubstituted or substituted by one or more R_(g);R_(g) is selected from the group consisting of C1-3 alkyl, phenylunsubstituted or substituted by halogen or methyl; C1-3 alkoxy, aryloxy,benzyloxy, C1-3 alkoxycarbonyl, carbamoyl wherein the nitrogen atom isunsubstituted or independently mono or di-substituted by C1-3 alkyl orphenyl; C1-5 alkanoylamino, aroylamino, amino wherein the nitrogen atomis unsubstituted or independently mono or di-substituted by C1-3 alkylor phenyl; halogen, hydroxy, oxo, carboxy and cyano; R_(h) is selectedfrom the group consisting of C1-3 alkyl, phenyl, C1-3 alkoxycarbonyl,benzyloxy and carboxy; R₈ is a heteroaryl ring selected from the groupconsisting of oxazolyl, thiazolyl, imidazolyl, pyridyl, benzimidazolyl,benzthiazolyl and benzoxazolyl, wherein any of the above R₈ can beunsubstituted or substituted by one or more R_(j); R_(j) is selectedfrom the group consisting of C1-5 alkyl, cyclohexyl, phenyl,piperidinyl, furanyl, thienyl, pyridinyl, benzyl, methoxy, phenoxy,benzyloxy, methoxycarbonyl, acetyloxy, benzoyloxy, carbamoyl wherein thenitrogen atom is unsubstituted or independantly mono or di-substitutedby methyl, phenyl, furanyl or thienyl; acetylamino, benzoylamino, ureidowherein either nitrogen atom is unsubstituted or independentlysubstituted by methyl or phenyl; methoxycarbonylamino, C1-3alkylsulfonylamino, arylsulfonylamino, amino wherein the nitrogen atomis unsubstituted or independently mono or di-susbstituted by methyl,phenyl, furanyl or thienyl; halogen, hydroxy, carboxy and cyano, R_(j)is unsubstituted or substituted by one or more R_(k); R_(k) is selectedfrom the group consisting of methyl, C5-6 cycloalkyl, phenyl,piperidinyl, piperazinyl, furanyl, thienyl, C1-3 alkoxy, phenoxy,benzyloxy, methoxycarbonyl, acetyloxy, benzoyloxy, carbamoyl wherein thenitrogen atom is unsubstituted or independantly mono or di-substitutedby methyl or phenyl; acetylamino, benzoylamino, ureido wherein eithernitrogen atom is unsubstituted or independently substituted by methyl orphenyl; benzyloxycarbonylamino, benzyloxycarbonylamino C1-5alkyl, aminowherein the nitrogen atom is unsubstituted or independently mono ordi-substituted by C1-3 alkyl, phenyl, furanyl or thienyl; halogen,hydroxy, carboxy, cyano and nitro, wherein R_(k) is unsubstituted orsubstituted by R₁; and R₁ is selected from the group consisting ofmethyl, C3-6 cycloalkyl and phenyl.
 18. The compound according to claim17 wherein: A is —C(O)— or —SO₂—; R₁ is piperidinyl or piperazinyl,wherein R1 is unsubstituted or substituted by one or more R_(b); R_(b)is selected from the group consisting of C1-3 alkyl, C5-6 cycloalkyl,phenyl, furanyl, thienyl, pyrrolyl, imidazolyl, indolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, C1-3 alkoxy,C1-3 alkoxycarbonyl, carbamoyl wherein the nitrogen atom isunsubstituted or independently mono or di-substituted by C1-3 alkyl orphenyl; C1-5 alkanoylamino, aroylamino, C1-5 alkylsulfonylamino,arylsulfonylamino, amino wherein the nitrogen atom is unsubstituted orindependently mono or di-substituted by C1-3 alkyl; halogen, hydroxy,oxo, carboxy and cyano, R_(b) is unsubstituted or substituted by one ormore R_(c); R_(c) is selected from the group consisting of C1-3 alkoxy,halogen and hydroxy; R₃ is C1-5 alkyl or C5-6 cycloalkyl, wherein R₃ isunsubstituted or substituted by one or more R_(d); R_(d) is selectedfrom the group consisting of methyl, C3-6 cycloalkyl, phenyl, thienyl,imidazolyl, pyridinyl, indolyl, C1-4 alkoxy, C1-5 alkanoylamino,methylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, halogen, hydroxy, oxo, carboxy and cyano, R_(d) isunsubstituted or substituted by one or more R_(e); R_(e) is selectedfrom the group consisting of methyl, phenyl, benzyl, methoxy, phenoxy,benzyloxy, benzoyl, halogen and hydroxy; R_(f) is selected from thegroup consisting of C3-6 cycloalkyl, phenyl, naphthyl, thienyl,imidazolyl, pyridinyl, indolyl, methoxy, benzyloxy, C1-3 alkanoylamino,methylthio wherein the sulfur atom is unoxidized or oxidized to asulfoxide or sulfone, benzylthio wherein the sulfur atom is unoxidizedor oxidized to a sulfoxide or sulfone, methoxycarbonylamino, aminowherein the nitrogen atom is unsubstituted or independently mono ordi-substituted by C1-3 alkyl; halogen, hydroxy, carboxy and cyano, R_(f)is unsubstituted or substituted by one or more R_(g); R_(g) is selectedfrom the group consisting of methyl, phenyl unsubstituted or substitutedby halogen or methyl; methoxy, phenoxy, benzyloxy, methoxycarbonyl,amino wherein the nitrogen atom is unsubstituted or independently monoor di-substituted by C1-3 alkyl or phenyl; halogen, hydroxy and carboxy;R₈ is a heteroaryl ring selected from the group consisting of oxazolyl,thiazolyl, imidazolyl, pyridyl, benzthiazolyl and benzoxazolyl, whereinany of the above R₈ can be unsubstituted or substituted by one or moreR_(j); R_(j) is selected from the group consisting of C1-5 alkyl,phenyl, furanyl, thienyl, piperidinyl, pyridinyl, benzyl, methoxy,methoxycarbonyl, acetyloxy, benzoyloxy, carbamoyl wherein the nitrogenatom is unsubstituted or independantly mono or di-substituted by methylor phenyl; acetylamino, benzoylamino, ureido wherein either nitrogenatom is unsubstituted or independently substituted by methyl or phenyl;methoxycarbonylamino, amino wherein the nitrogen atom is unsubstitutedor independently mono or di-substituted by methyl or phenyl; halogen,hydroxy, carboxy and cyano, R_(j) is unsubstituted or substituted by oneor more R_(k); and R_(k) is selected from the group consisting ofmethyl, C5-6 cycloalkyl, phenyl, piperidinyl, methoxy, phenoxy,benzyloxy, methoxycarbonyl, carbamoyl wherein the nitrogen atom isunsubstituted or independantly mono or di-substituted by methyl orphenyl; ureido wherein either nitrogen atom is unsubstituted orindependently substituted by methyl or phenyl; benzyloxycarbonylamino,benzyloxycarbonylaminoC1-5alkyl, amino wherein the nitrogen atom isunsubstituted or independently mono or di-substituted by C1-3alkyl,phenyl, furanyl or thienyl; halogen, hydroxy, carboxy, cyano and nitro,wherein R_(k) is unsubstituted or substituted by R₁; R₁ is selected fromthe group consisting of methyl and phenyl.
 19. The compound according toclaim 18 wherein: R_(b) is selected from the group consisting of,pyrrolyl, imidazolyl, indolyl, benzimidazolyl, methoxy, methoxycarbonyl,amino wherein the nitrogen atom is unsubstituted or independently monoor di-substituted by C1-3 alkyl; halogen, hydroxy and carboxy, R_(b) isunsubstituted or substituted by one or more R_(c); R_(c) is selectedfrom the group consisting of methoxy, halogen and hydroxy; R_(d) isselected from the group consisting of methyl, C3-6 cycloalkyl, phenyl,C1-4 alkoxy, C1-3 alkanoylamino, methylthio wherein the sulfur atom isunoxidized or oxidized to a sulfoxide or sulfone, halogen, hydroxy, oxo,carboxy and cyano, R_(d) is unsubstituted or substituted by one or moreR_(e); R_(e) is selected from the group consisting of methyl, phenyl,methoxy, halogen and hydroxy; R₅ is H; R_(f) is selected from the groupconsisting of C5-6 cycloalkyl, phenyl, naphthyl, thienyl, indolyl,methoxy, methylthio wherein the sulfur atom is unoxidized or oxidized toa sulfoxide or sulfone, methoxycarbonylamino, halogen, hydroxy, carboxyand cyano, R_(f) is unsubstituted or substituted by one or more R_(g);R_(g) is selected from the group consisting of methyl, phenylunsubstituted or substituted by halogen; methoxy, phenoxy, benzyloxy,methoxycarbonyl, halogen, hydroxy and carboxy; R₈ is a heteroaryl ringselected from the group consisting of oxazolyl, pyridyl, benzthiazolyland benzoxazolyl, wherein any of the above R₈ can be unsubstituted orsubstituted by one or more R_(j); R_(j) is selected from the groupconsisting of C1-5 alkyl, phenyl, piperidinyl, pyridinyl, benzyl,methoxy, methoxycarbonyl, acetyloxy, benzoyloxy, carbamoyl wherein thenitrogen atom is unsubstituted or independantly mono or di-susbstitutedby methyl or phenyl; methoxycarbonylamino, halogen, hydroxy and carboxy,R_(j) is unsubstituted or substituted by one or more R_(k); R_(k) isselected from the group consisting of methyl, C5-6 cycloalkyl, phenyl,piperidinyl, methoxy, methoxycarbonyl, carbamoyl wherein the nitrogenatom is unsubstituted or independantly mono or di-substituted by methylor phenyl; benzyloxycarbonylamino, amino wherein the nitrogen atom isunsubstituted or independently mono or di-substituted by methyl orphenyl; halogen, hydroxy and carboxy.
 20. The compound according toclaim 9 wherein: R_(b) is selected from the group consisting ofbenzimidazolyl, methoxy and dimethylamino, R_(b) is unsubstituted orsubstituted by a halogen atom; R₃ is C1-5 alkyl wherein R₃ isunsubstituted or substituted by one or more R_(d); R_(d) is selectedfrom the group consisting of C3-6 cycloalkyl and phenyl, R_(d) isunsubstituted or substituted by one or more R_(e); R_(e) is selectedfrom the group consisting of methyl and halogen; R₆ is C1-5 alkylunsubstituted or substituted by one or more R_(f); R_(f) is selectedfrom the group consisting of C5-6 cycloalkyl, phenyl, methylthio whereinthe sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone andhalogen, R_(f) is unsubstituted or substituted by one or more R_(g);R_(g) is selected from the group consisting of methyl, methoxy,methoxycarbonyl, halogen and hydroxy; R_(j) is selected from the groupconsisting of C1-5 alkyl, phenyl, pyridinyl, piperidinyl,methoxycarbonyl, carbamoyl wherein the nitrogen atom is unsubstituted orindependantly mono or disubstituted by methyl or phenyl;methoxycarbonylamino and halogen, R_(j) is unsubstituted or substitutedby one or more R_(k); R_(k) is selected from the group consisting ofmethyl, C5-6 cycloalkyl, phenyl, methoxycarbonyl, carbamoyl,benzyloxycarbonylamino and halogen.
 21. A method of making a compound ofthe formula(I)

wherein A is —C(O)—, X is O, R₇ is R₈—C(O)— and R₁, R₂, R₃, R₄, R₅, R₆and R₈ are as defined in claim 1; comprising a) coupling a protectedamino acid with N,O-dimethylhydroxylamine under coupling conditions in asuitable solvent to give the corresponding amide below:

wherein R″ is an amino protecting group, and R′ is NMe(OMe); b) reducingthe compound produced in a step a) with a reducing agent in a suitablesolvent to form a compound of the formula (V):

d) reacting a heterocycle R₈ according to claim 1, with n-BuLi to form acorresponding heterocyclic anion in a suitable solvent at a temperatureabout −30 to −100° C.; reacting the heterocycle R₈ anion with a compoundof formula V; e) removing the protecting group R″ from the compoundproduced in step d) and subsequently coupling with a compound of theformula(IV) under coupling conditions to produce a compound of theformula (VII):

and f) oxidizing compound VII from step e) to produce a compound of theformula(I).
 22. A pharmaceutical composition comprising apharmaceutically effective amount of a compound according to claims 1 or11 and one or more pharmaceutically acceptable carriers or adjuvants.23. A method of modulating an autoimmune disease, said method comprisingadministering to a patient in need of such treatment a pharmaceuticallyeffect amount of a compound according to claims 1 or
 11. 24. The methodaccording to claim 23 wherein the autoimmune disease is selected fromthe group consisting of: rheumatoid arthritis, systemic lupuserythematosus, Crohn's disease, ulcerative colitis, multiple sclerosis,Guillain-Barre syndrome, psoriasis, Grave's disease, myasthenia gravis,scleroderma, glomerulonephritis, atopic dermatitis and insulin-dependentdiabetes mellitus.
 25. A method of treating Alzheimer's diseasecomprising administering to a patient in need of such treatment apharmaceutically effective amount of a compound according to claims 1 or11.
 26. A method of treating atherosclerosis comprising administering toa patient in need of such treatment a pharmaceutically effective amountof a compound according to claims 1 or 11.